Clinical Toxicology

Toxicology

• Science of Poison (MOT)

• Branch of pharmacology
• Which deals with undesirable effects of chemicals on living systems, from individual cells to complex
ecosystems. MTC → MINIMUM TOXIC CONCENTRATION

PARACELSUS → “All substances are poisons, there is none which is not poison,
PHILIPPUS AUREOLUS the right dose differentiates a poison from a remedy”
THEOPHRASTUS BOMBASTUS
VON HOHENHEIM
MARTHIEU ORFILIA → Modern father of toxicology (Quantification)
→ His Traite des poisons, also called Toxicologiegenerale
→ MARSH TEST → TEST FOR ARSENIC
LEX CORNELIA → First book regarding poisoning

When the drug reaches the MTC → the drug will produce undesirable effects
Main concern: study the mechanism of toxicity (MOT)
PARA → all drugs are poison it is just a matter of dose; the dose differentiates the poison with the drugs = e.g.
increase dose = increase toxicity → poison

Mathieu → discovered the test for arsenic which is known as Marsh test (a quantitative test for arsenic)

Poisons

• Corpus delecti (body of evidence)

• Any agent which may cause serious body injury, disease or death when applied, introduced into, or
developed within the body

Any substance that produces undesirable effect especially → serious body injury = poison

Body of evidence → can be used to determine or solve a crime to investigate

TERM KEY WORDS

INTOXICATION Toxicity associated with any chemical substance
A. POISONING A clinical toxicity secondary to accidental exposure
B. OVERDOSE An intentional exposurewith the intent of causing self-injury or
death
HAZARD Likelihood that will occur in a given situation or setting
RISK Expected frequency of the occurrence of an undesirable effect
arising from exposure to a chemical or physical agent
Intox → whether it is accidental or intentional = if there will be toxicity associate with chemical substances
= INTOXICATION
Poisoning → e.g. exposed to certain chemical accidentally
Overdose → intentional
Hazard → Can substance cause toxicity or not? – Can intoxication can occur once given with this substance
Risk → How frequent a drug will produce its toxicity?

AREAS OF TOXICOLOGY

1. MAIN AREAS
• Descriptive
• Mechanistic
• Regulatory

2. SPECIALIZED AREAS
• Forensic
• Environmental
• Clinical
• Occupational

MAIN AREAS
DESCRIPTIVE → concerned with toxicity testing, which provides necessary
(WHAT ARE THE TOXIC EFFECTS information for safety evaluation & regulatory requirements
OF POISON?)
MECHANISTIC → elucidates MOT
REGULATORY (DESCRIPTIVE + → decides whether the drug dose is safe or not
MECHANISTIC) → DECISION MAKING

Mechanistic → how the poison causes undesirable effects? → HOW; what is the MOT of this substance
Regulatory → combination of descriptive and mechanistic; involves decision making bcs → decides if the
drug is safe or not to be given to a patient; based on the information from descriptive and mechanistic
toxicology
 SPECIALIZED AREA
FORENSIC (ANALYTICAL → medicolegal aspect, criminal investigation
CHEMISTRY + CLINICAL
TOXICOLOGY)
ENVIRONMENTAL → deals with the potentially deleterious impact of chemicals,
present as pollutants of the environments, to living organism
→ ZOOTOXINS, PHYTOTOXINS, MICROBIAAL TOXINS
EXPERIMENTAL →BIOASSAYS, Laboratory testing. Use of different reagents
→ LD50 → LETHAL DOSE 50
→ LC50 → LETHAL CONCENTRATION 50
→ TLC → THRESHOLD LIMIT CONCENTRATION
→ TLV → THRESHOLD LIMIT VALUE
CLINICAL →realm of medical science
→ DIAGNOSIS AND TREATMENT
→ Overdose vs. Drugs for abuse vs household products
OCCUPATIONAL → protect workers form hazards found in workplace

Forensic → a hybrid of analytical chemistry and clinical toxicology; hence, body of evidence used in medicolegal
aspects
Envi → toxins found in the environment → presents as pollutants of the environment/living organisms
Zoo – animal. Phyto – plants, microbial – microorganisms

PARAMETERS USED IN THE BIOASSAYS FOR EXPERIMENTAL TOXICOLOGY

LD 50 – dose that can cause death to the 50% of the population
LC 50 - concentration that can cause death to the 50% of the population
TLC – threshold limit concentration – TLV- threshold limit value

Clinical → tx after identifying that the drug is toxic; drugs for dx and tx of substance

Occupational → long term exposure to these chemicals will produce undesirable effects → protection

POISONS SOURCES
Tetrodotoxin Puffer fishes (SEIZURE) (BENZODIAZEPAM, CALCIUM GLUCONATE,
PROPRAANOLOL)
Cantharidin Blister fly/Spanish fly (APHRODISIAC)
Clupeotoxin Oyster, sardines (Venerupin),, anchovies (SHARP METALLIC TASTE)
(ABDOMINAL PAIN, VOMITING, DIARRHEA)
Scromboid toxin Tuna (Saurine)
Mackarel (Gemblid) (CONFUSED MSG REACTION) (FLUSHING,
NUMBNES, BURNING)
Ciguatoxin Fish organs (liver) (MOST COMMON POISON FROM INGESTED
FROM) (Gambierdicustoxicus)

ZOOtoxins → toxins found in animals

Puffer fish – butete; specific in blocking the Na channel → therefore → causing seizures; potent toxin that is
capable of causing seizures (TX: benzodiazepines, Ca Gluconate, and Propranolol)
Cantharidin → used as an aphrodisiac/ stimulate sexual desire
Clupeotoxin → has sharp metallic taste → causing abdominal pain, vomiting, & diarrhea
Scromboid → confused with MSG (monosodium glutamate) reaction → symptoms: flushing, numbness, burning
sensation
Ciguatoxin → most common poison from ingested fish; produced by Gambierdicus toxicus

Latrotoxin Black widow spider/Hourglass spider

(Latrodectusmactans) (15 times stronger than rattlesnake)
5-hydroxytryptamine Scorpion (Centuroidessculpturatus)
(serotonin)
Bee venom Hymenoptera (bee, wasps, ants)
Hyalunoridase Snakes
(spreading factor)

Hyaluronidase → also called as spreading factor because it helps on spreading the toxin the body → some
bacteria have these enzymes → spread rapidly
RED SQUILL →Urginea maritime → effective in controlling rodents

PATULIN → ROTTEN APPLE

Patulin not a zootoxin but rather a PHYTOtoxin

POISON SOURCE/S
Arecoline Betel nut (Areca catechu)
Brucine → GLYCINE INHIBITOR Nux vomica
(INCREASE THE NT) (SEIZURE)
Strychnine → PESTICIDE (SEIZURE)
Picrotoxin→ GABA A ANTAGONIST → Fish berries
CONVULSANT Equimolar mixture of two compounds, picrotoxin
and picrotin
Myristicin Nutmeg (HALLUCINOGENIC SUBSTANCE OF
POISON INMATES)
Cicutoxin Water hemlock Cicutadouglasii
Colchicines (ACUTE GOUT) Autumn crocus
ALLOPURINOL (CHRONIC GOUT)

Nicotinic acid base alkaloid coming from Areca catechu

Brucine → example of a glycine inhibitor → increase the amount of NT → that may cause seizure
Strychnine → pesticide and particularly in killing small vertebrates such as birds and rodents → can also cause
seizures bcs it is a potent convulsant drug
Picrotoxin → non-competitive antagonist of GABA-A and a convulsant drug (a drug that may cause seizure) bcs
of the inc. in NT
- Combination of picrotoxinin and picrotin

Myristicin → nutmeg → used as a hallucinogenic substance of poison inmates

Convallarin Lily of the valley Convallariamajalis
Coniine (POISON THAT KILLED SOCRATES) Poison hemlock Conium maculatum
Phenanthridine Daffodil, jonquil Narcissus pseudonarcissus
Podophyllotoxin American mandrake, May apple
Podophyllumpeltatum
 • The flower heads of chrysanthemum - pyrethrins (INSECTICIDE)
• mycotoxin found in claviceps purpurea – ergot
• from potatoes – solanine
• manihotoxin-cassava
• benzopyrene in smoke

Pyrethrins → used as an insecticide

Mycotoxin → fungi in the rye

MUSHROOM TOXINS

“AY OMG May Cabute Pala”

Group Toxin EFFECT

I Amanitotoxins, cyclopeptides hepatotoxins
IA Orellanine, orelline nephrotoxins
II Muscimo, iboteric acid Hallucinogens, anticholinergic
signs and symptoms
 III gyrometrin Hepatotoxin
Hydrolyzes to form
monomethylhydrazine
IV muscarine Cholinergic overstimulation
V coprine Disulfiram reaction
VI Psilocin, psilocynbin hallucinogens

Hallucinogens → can cause deliriums, anticholinergic sypmtoms

CHOLINERGIC overstimulation/cholinergic overdose → DUMBBELSS

DISULFIRAM REACTION:

• Flushing or redness of the skin (VASODILATION)

• Shortness of breath
• Nausea
• Vomiting
• Headache
• Cholinergic overdosage
• Diarrhea
• Urination
• Miosis
• Bradycardia
• Bronchoconstriction
• Emesis
• Lacrimation
• Salvation
• Sweating

MICROBIAL TOXINS

Poison Source
Saxitoxin Dinoflagellates
Aflatoxin (PEANUTS) Asperigullus flavus
ptomaine Bacterial decay (SPOILED FOOD)
Tyrotoxicon Bacterial decay (MILK)
Ergot (ERGOTAMINE AND ERGOVALINE) Claviceps purpurea
Exotoxins Mostly from gram (+)
Botulinum toxin FLACCID PARALYSIS C. botulinum
Tetanospasmin SPATIC PARALYSIS C. tetani
ALPHA toxin / LECITHINASE C. perfringens → GAS GANGRENE

Commonly present on spoiled food, milk

Stale peanuts
C. perfringens → causative agent of gas gangrene
 POISONING EFFECTS

POISON EFFECT SITE OF ACTION EXAMPLES

Local ON the site of contact CORROSIVES
Remote OTHER than the site of contact ATRIOPINE taken orally
Combination BOTH PHOSPORUS CANTHARIDIN

Corrosive → acids and bases

Remote → e.g. hands contact → manifesting on other parts of the body; atropine → can cause systemic effects

FACTORS AFFECTING POISONING EFFECT

POISON RELATED

• Route of administration
• Concentration
• Solubility

PATIENT RELATED
• Age
• Habit
• Idiosyncracy
• Tolerance
INJECTED POISON
IV → INHALATION → SUBSCUTANEOUS -→ POLAR SOLVENTS

WATER SOLUBLE DRUGS → POLAR SOLVENTS

LIPID SOLUBLE DRUGS -→ NON-POLAR SOLVENTS
Injected poisons are more toxic than oral;
Severity of toxicity of dif. route of administration: IV → inhalation → SQ → oral → dermal

Con → as the conc. increase = chance of toxicity also increases

Water soluble drugs are more toxic in polar solvents

Lipid soluble drugs are more toxic in non-polar solvents

Age → more toxic to children and elderly; children → underdeveloped organs; elderly → deteriorating organs
Some drugs → habit forming esp. dangerous drugs → can cause addictions
Idiosyncrasy → irregular reaction of the body with the drugs
Tolerance → down grade regulation of the receptors → decrease in the responsiveness of the body to a certain
drugs through repetitive exposure; increase responsiveness = increase dosing

TYPES OF POISONING
TYPE MANIFESTATION
 ACUTE Prompt and there is marked
ddisturbances of function or death within
a short period of time
CHRONIC Gradual and there is progressive
deterioration of the functioning of tissues
CUMMULATIVE Increases in its intensity of action when a
certain limit is reached

Examples:

ACUTE

1. Taking a strong poison

2. Excessive single dose of a drug
3. Several small doses but frequent administration of drugs

CHRONIC

1. Taking several small doses of drugs at long intervals

2. Taking only toxic doses of the drug

CUMMULATIVE

1. Intake of metal compounds

Acute → right after the exposure or with a short period of time

Chronic → long term
Cumulative → when a certain level is reached = increase intensity of action

DURATION AND FREQUENCY OF EXPOSURE

Type of EXPOSURE FREQUENCY

Acute < 24 hours
Subacute < or = 1 month
Subchronic 1-3 months
Chronic 3 months
Repeated Dietary
Body is exposed with the substance in less than a day

THE TYPE OF POISONING (when did the drugs take effect) AND TYPE OF EXPOSURE (how long and freq is the
exposure)
 WHAT ARE THE EVIDENCES OF POSONING?

EVIDENCE OF POISONING DESCRIPTION

CIRCUMSTANTIAL Deduced from various events or facts.
Not a strong evidence
POST-MORTEN Gathered after an autopsy is performed
EXPERIMENTAL Administering the suspected substance to some
living animal and noting the effects of samples of
body fluids collected
SYMPTOMATIC Poisoning signs or effects are observed

Post-mortem → what is the cause of death, what is the condition of the tissues after the autopsy; one of the strong
evidence of poisoning
Experimental → the cause of the toxicity that causes of death → ipapainom
Chem → volumetric analysis

QUIZ

1. The Father of Modern Toxicology

2. An intentional exposure with the intent of causing self injury or death
3. A poison that killed Socrates
4. Puffer fish toxin.
5. A toxin used as aphrodisiac
6. A poisoning that is gradual & there is progressive deterioration of the functioning of tissues
7. It causes flaccid paralysis.
8. Frequency of Sub-acute toxicity.
9. Gathered after an autopsy is performed
10. Toxin in red tide poisoning.
11. Class 4 mushroom toxin associated with cholinergic overstimulation.
12. Hallucinogenic substance of poison inmates
13. This is produced from Gambierdiscus toxicus HOUSEHOLD TOXICOLOGY
14. It involves decision-making, based on the information provided by the descriptive and
mechanistic toxicology, whether a chemical possesses a sufficiently low and safe dose to be
marketed for its purpose
15. A toxin from black widow spider.
16. AKA venom spreading factor.
17. The likelihood that injury will occur in a given situation or setting
18. Frequency of Sub-acute toxicity.
19. Paracelsus True name
20. Scientific name of the source of Nicotine

ANSWERS:
Mathieu, Overdose, Coniine, Tetrodotoxin, Catharidin, Chronic exposure, Botulinum toxin, < or equal to one month
Post mortem, Saxitoxin, Muscarine, Myristicin, Ciguatoxin
General Management of Poisoned Patient

⚫ Initial Assessment
⚫ Evaluate and support
⚫ A-irway
⚫ B-Breathing
⚫ C-Circulation
⚫ D-extrose
⚫ Decontamination

✓Decontamination
• One of the most dangerous
• Tx-rapid removal from the environment • If necessary :100% O2, assisted ventilation, brochodilators

✓Ocular Exposures
• NSS irrigation for 15 mins

✓Dermal Exposures
• Removed contaminated materials from the patient

Most dangerous because → inside the internal system of the body

usually poisoned patients → decrease oxygen level/ hypoxia → admi 100% O2 or hyperbaric oxygen
BD → beta antagonist
Ocular → substance is exposed in the ophthalmic → eyes
Dermal → more easily removed → skin only

GENERAL TYPES OF ANTIDOTES

PHYSIOLOGIC MOT: Functional antagonism
Produce an opposite effect as that of the poison
EXAMPLES
Ethanol + Caffeine
Atropine + Physostigmine/Neostigmine
Isoniazid + BZD
CHEMICAL MOT: Chemical antagonism
Change the structure of the poison
EXAMPLES
CN toxicity + Sodium thiosulfate → SCN
MECHANCAL A. Gastric Lavage
B. Emesis
C. Activated Charcoal
D. Laxatives/Cathartics E. Hemodialysis
F. Hemoperfusion G. Forced Diuresis
H. Urinary pH manipulation

Functional because → effects of the drugs esp. the opposite e.g. ethanol (CNS depressant → administer CNS
stimulant → caffeine (1,3,7-trimethylxanthine) = producing opposite effect
Atropine (anti-choli) + -stigmine (cholinergic) = in terms of
-atropine poisoning (anti-choli) → antidote: PHYSOSTIGMINE;
-in terms of cholinergic poisoning: atropine;
-*neostigmine or pyri → antidote for neuromuscular esp. non-depo TUBOCURARINE (-curare effects)

INH (can cause seizure → administer BZD antiseizure)

SCN → thiocyanate – non-toxic and easily secreted by the body

CHEMICAL → goal: change the STRUCTURE of the poison → *common examples: metal toxicity, chelates,
deferoxamine, EDTA, etc.

Mechanical → removal of substances in the body

 MEHCANICAL ANTIDOTE

1. GASTRIC LAVAGE
⚫ For patients that are unconscious/ no gag reflex
⚫ Massive ingestions
⚫ C/I:
- Acids and alkali or hydrocarbons
- Combative patients

Gag reflex → reflex mechanism of the body; (The gag reflex, also called the pharyngeal reflex, is a contraction
of the throat that happens when something touches the roof of your mouth, the back of your tongue or throat,
or the area around your tonsils)
CI: acids & alkalis or hydrocarbons intoxication → will cause damage in the internal organs such as esophagus,
stomach
Combative → have high gag reflex

2. EMESIS
⚫ Syrup of Ipecac - May be used in the case of ingested non-corrosive toxins, this may involve
inducing vomiting (emesis) if the patient is conscious.
⚫ A/E:
⚫ Mallory Weiss Tear → Hemorrhagic gastritis

Emesis → induce vomiting

CONSCIOUS AND GASTRIC LAVAGE IS C/I OR NOT SUITABLE
Syrup of ipecac available as fluidextract and 40x more toxic & more potent than ipecac syrup; Ipecac → Cephaelis
ipecachuana
Mallory Weiss tear → tear in the mucous membrane or inner lining between esophagus and stomach; may cause
hemorrhagic gastritis (inflammation and bleeding in the part between esophagus and stomach) → bcs of the
tearing in the mucous membrane

Doses of IPECAC

Age Dose (ml)

6-9 months 5
9-12 months 10
1-12 years 15
>12 years 30

Ipecac is not indicated for patients less than 6 months; only for 6 months and above; ages = dose increases directly

Contraindications
✓ Children shuller o months of age
✓With CNS depression/seizures
✓ Strong Avid, alkali or sharp object ingespon
✓With compromised airway protective reflexes
✓ Ingestion of some types of hydrocarbons or petroleum distillates
✓ Ingestion of substances with extremely rapid onset of action
✓With emesis following of ingestion
Seizures = C/I because it can cause seizures
Strong acid, alkali, or syrup → x be vomited/induce emesis → damage the internal organs e.g. esophagus and
stomach
Cannot induce emesis in patients → that have toxicity symptoms of vomiting = too much emesis = Mallory Weiss
tear
SIGNS AND SYMPTOMS
VOMITIOUS SUBTANCE/S
Blue-green Copper

Ground coffee Sulfuric acid

Luminous vomit Phosphorus, arsenic

Yellow green Chromium

Milky vomitus Lead

SUBSTANCE ASSOCIATED WITH THE VOMITOUS/CAUSES

3. CATHARTICS
• Induce evacuation of bowel

4. PRECIPITANTS
• Alter the poison by forming an insoluble substance

CO and MO are commonly used for phenol intoxication

Ethylene glycol toxicity → antidote: calcium gluconate = producing calcium oxalate that prevents the formation
of oxalic acid (accumulation of oxalic acid = inflammation of the bladder/kidney)
5. ADSORBENTS
• ACTIVATED CHARCOAL-Universal Antidote
Dose
Children: 1-12 years: 25-50g up to 1 year: 1g/kg Adults: 25-100g
Cyanide Ethylene Glycol
Ethanol Methanol
Lithium Organic solvent
Lead Potassium
Iron Strong acids
Mercury Strong alkali
CELLIME MOPSS → antidote: activated charcoal with the doses:

CHELATING AGENTS
DIMERCAPROL As, Hg, Pb, Sb, British Anti-Lewisite, BAL (2,3
Au, Bi Dimercaptopropanol) - serves
as the metal acceptor &
prevents binding of
the-SH groups of enzymes to
metals
-IM (peanut oil)
- C/1: Fe, Cd, Se
EDETATE CALCIUM DISODIUM Pb, Mn, ZN →Ethylene diamine tetraacetic
(EDTA) acid
→ IV/IM
UNITHIOL Hg and As toxicity → Dimercaptopropanesulfonic
acid (DMPS)
→ IV
PENICILLAMINE Copper Toxicity D-dimethyl cysteine

DEFEROXAMINE Iron →Source: Streptomyces pilosus

 Treatment of Iron toxicity
DEFERASIROX
→ tridentate chelator with high
affinity to iron
PRUSSIAN BLUE Cesium and Thallium toxicity Ferric Hexacyanoferrate/ Ferric
Ferrocyanide

Chelating agents most common in metal toxicity; Chelating agents have the ability to bind with metal to
decrease metal absorption in the body
AKA BAL; chemical name: 2,3 –Dimercaptopropanol
When the –SH groups (thiol) of enzymes bind to metal = cause hypoxia → leading to metal toxicity → BAL
prevents this process
Available in non-aqueous solution → because aq. soln are unstable forms → therefore solvent: oil esp.
PEANUT OIL administered IM
C/I: Fe, Cd, Se toxicity

EDTA → salt form for EDTA: Edetate Calcium disodium

Unithiol administered IV → and better than BAL for Hg and As toxicity

Chem name: DMPS

Penicillamine → Cu toxicity esp. Wilson’s toxicity

AKA D-dimethyl cysteine
Wilson’s → autosomal recessive inherited disorder of copper metabolism → difficulty in the metabolism of
Cu → accumulation = Cu toxicity

Deferoxamine → can also be used in the treatment of aluminum toxicity together with hemodialysis
Deferoxamine + hemodialysis = treatment for aluminum toxicity

Turnbull’s blue → ferrous ferricyanide (not used in metal toxicity only → Prussian blue)

WHOLE BOWEL IRRIGATION

• Use PEG (Golytely,Colyte)
• dosage: 1-2 L/hr (PO or by NGT)

INDICATION:
⚫ Poorly absorbed substances (Fe, Pb, Li)
⚫ OSR preparations
⚫ Body packers/ illicit drugs
⚫ Later presentation

PEG – polyethylene glycol

SR preparation → sustained release

FORCED DIURESIS & URINARY MANIPULATION

• For substances whose elimination is primarily renal, relatively small volume of distribution with little
protein binding

ANTIDOTE TOXICITY
NaHCO3 Salicylic acid,
Phenobarbital
NH4CI, Vit C, HCI Amphetamine,
Phencyclidine, Strychnine, Quinidine/Quinine
 NaHCO3 (basic) + toxicity of acidic drugs (salicylic acid, phenobarbital) = salt and water → excretion
RATIONALE: Acidic antidote for basic toxicity – acidic urination; basic antidote for acidic toxicity – basic
urination = excretion

EXTRACORPOREAL METHODS

HEMODIALYSIS
⚫ Water-soluble
⚫ Small volume of distribution (<0.5
⚫ L/Kg)
⚫ Low MW (<500 daltons)
⚫ Not significantly bound to plasma proteins
INDICATIONS:
Ethylene glycol, Methanol,
Paraquat
Ethanol, Theophylline, Lithium, Salicylates, Long-acting Barbiturates
HEMODIALYSIS → meaning hence indication:
Herbicide – weed killer

HEMOPERFUSION
⚫ Passage of anticoagulated blood through a column containing activated charcoal or resin
particles
⚫ Advantage: faster thanhemodialysis
⚫ Disadvantage: does not correct fluid & electrolyte abnormalities
More effective:
Phenobarbital, Phenytoin, Carbamazepine, Methotrexate, Theophylline
Less effective:
Ethanol, Methanol
Disadv: unlike hemodialysis → which correct fluid and electrolyte abnormalities
If the toxic substance or drug is water soluble → hemodialysis is better
GENERAL TYPES OF TOXINS ACCORDING TO EFFECTS
• IRRITANTS → causes Inflammation of mucous membrane upon contact
1. Halogens
2. Hydrogen Chloride
3. Hydrogen Fluoride
4. Ammonia
5. Alkaline dust
6. Arsenic trioxide
7. Phosgene
8. Phosphorus Chlorides
9. Ozone
10. Nitrogen dioxide

• NEUROTICS → affects the CNS

1. Carbon disulphide
2. Organic phosphorus/ insecticides
3. Methyl mercury
4. Manganese
5. Tetraethyl lead
6. Thallium

Neurotics → substance that causes disturbances in the CNS

• CARCINOGENS → can initiate the proliferation of malignant neoplastic cells
1. Asbestos
2. Alpha-naphtylamine
3. Ethylene Oxide
4. Benzene
5. Benzopyrene

Can cause CA
Sunog na pagkain (contains benzene & beznzopyrene) = accumulation can cause CA/can initiation of the
proliferation of malignant neoplastic cells
• ASPHYXIANTS → susbtances that causes Dyspnea
1. Simple Asphyxiants gases that displaces Oxygen
1. Carbon dioxide
2. Helium
3. Nitrogen
4. Argon

2. Chemical Asphyxiants → interferes in the utilization of oxygen → Cellular Hypoxia

1. Carbon monoxide
2. Cyanide
3. Hydrogen sulfide
DYSPNEA → difficulty on breathing → leading to hypoxia
Simple and chemical = both causes OXYGEN DEPLETION → leading to hypoxia

• LACRIMATORS → stimulates the flow of tears, chemical agents used in Riot Control
1. Organophosphates

•STERNUTATORS → causes excessive sneezing

1. Veratrine → Veratrum alba

•ASTHENICS → produces muscular weakness

1. Neuromuscular blockers

• NARCOTICS → produces mental depression

1. Sedative Hypnotics (Opioid derivatives)
Cholinergics → organophosphates → that can cause lacrimation (DUMBBELSS)/ tearing of the eyes
Neuromuscular blockers → depolarizing (Succinylcholine) & nondepolarizing (curare e.g. tubocurarine,
pancu, atra, & vecuronium)
Narcotics like opioid → CNS depressants

EFFECT EXAMPLE
1. Irritants cause tissue ACIDS AND ALKALI
necrosis on contact
2. Neurotics affect the CNS HALLUCINOGENS

3. Carcinogenics stimulate growth of cancer INDUSTRIAL POISONS

cells

4. Asphyxiants cause dyspnea CO, METHANE

5. Lacrimators stimulate flow of tears ORGANOPHOSPHATES

6. Sternutator cause excessive sneezing VERATRINE

7. Asthenics produce muscular weakness NEUROMUSCULAR BLOCKERS

8. Narcotics mental weakness/ depression SEDATIVE HYPNOTICS

TOXI PART 3

HOUSEHOLD TOXICOLOGY

ETHYLENE GLYCOL

• ANTIFREEZE CHEMICAL
• MOT:
• ETHYLENE GLYCOL →glycol aldehyde →glycolic acid AND glyoxylic acid → ACIDOSIS
• Toxic metabolite: Oxalic Acid (KIDNEY)
• Treatment: Ethanol and Fomepizole (Antizol)

Toxic in the kidney

Antifreeze → lowers the freezing point of any chemical substance

Ethylene glycol
Fomepizole (antizole) or ethanol
Alcohol Dehydrogenase (ADH) (+)
(Both competitive inhibition)
Glycolaldehyde

Aldehyde dehydrogenase (ALDH)

Glycolic acid (glycolate)

Glycolic acid

_________ Oxalic acid __________

𝜕-Hydroxy-𝛽-Ketoadipic acid +Ca + _______ acid

Calcium oxalate
MOST TOXIC METABOLITE: Oxalic acid → toxic in the kidney
ANTIDOTES:
Fomepizole (ADH inhibitor → preventing the conversion of ethylene glycol to glycoaldehyde → x conversion of
ethylene glycol → OXALIC ACID (toxic metabolite)
Ethanol → competitive inhibitor of ethylene glycol → rationale: (+) ethylene glycol poisoning → when
administered with ethanol → the shift of focus now of ADH to ethanol → preventing the further conversion of
toxic metabolite for ethylene glycol

METHANOL

• FOUND IN THE FORM OF CANNED HEAT OR IN WINDSHIELD PRODUCT

 • DESTRUCTIVE DISTILLATION OF WOOD →WOOD ALCOHOL CH30H
• DENATURANT
• PAINT REMOVER
• VISUAL DISTURBANCES, METABOLIC ACIDOSIS
• MOT:
• METHANOL →FORMALDEHYDE(BLINDNESS) → FORMICACID →ACIDOSIS
• TEST: Lieben'slodoform - Yellow ↓
UNDERGONE DESTRUCTIVE DISTILLATION
Toxicities: visual disturbances and metabolic acidosis
Blindness because of the toxic metabolite → formaldehyde; metabolic acidosis because of formic acid
2 metabolites: formaldehyde (blindness), formic acid (metabolic acidosis)
YELLOW PPT
ANTIDOTE: Fomepizole and ethanol

FOMEPIZOLE → INH. ALCOHOL DEHYDROGENASEETHANOL → SHIFT OF FOCUS OF

ALCOHOLDEHYDROGENASE

ACETONE

• Primary ingredient in fingernail polish remover, airplane glues, varnish, & rubber cement
• SOLVENT FOR SYNTHESIS OF SHABU/METHAMPHETAMINE
• Signs & symptoms:

-CNS depression → coma, respiratory depression

- treatment: neutralization with milk or water

TEST: Benzoldt Gunning → (+) indigotine

Antidote: neutralization of acetone with milk and water

FORMALDEHYDE

• A.K.A FORMALIN, FORMOL

• EMBALMING AGENT
• SIMILAR PRESENTATION WITH METHANOL TOXICITY
• Signs & symptoms:
 - local: mucosal irritation

- systemic: CNS depression, coma, metabolic acidosis

• MOT:

FORMALDEHYDE(BLINDNESS) →FORMIC ACID →ACIDOSIS

Treatment: Ammonia &NaHCO

One of the metabolites of methanol → formaldehyde →causing blindness or visual disturbances
Treatment of acidosis → administration of base: AMMONIA and sodium bicarbonate

HYDROCARBONS

• Hydrocarbons →Benzene, Toluene (Methyl benzene),Xylene (Dimethyl benzene)

• Mostly derived from petroleum distillation
• Gasoline, kerosene
• Treatment:

-Emesis, Gastric lavage, Adsorption, Mineral oil

• MOT:
• HYDROCARBONS CANNOT BE METABOLIZED INTHE BODY →CNS DEPRESSION
GASOLINE & KEROSENE → where the HC were derived
MO – cathartics → most commonly used treatment: adsorption and cathartics → because gastric lavage and
emesis are sometime C/I with certain HC

CYANIDE

EX. Odor of bitter almonds, cherry red blood

• MOT: METHEMOGLOBINEMIA
• Inhibits cytochrome oxidase & prevents cellular respiration
• A: Amyl nitrite (Inhalation), Na nitrite, Na thiosulfate (IV), Dicobalt edentate (Kelocyanor),
Hydroxycobalamine→Vit B12
• TEST: Pirate test > (Yellow ↓)

• Schonbien-Pagenstecher> (+) Deep blue

Once cytochrome oxidase → inhibited → leading to hypoxia
→ prevent cellular respiration → accumulation of CN:
METHEMOGLOBINEMIA (common manifestation)
X (NO) cellular respiration = Hemoglobin (O2 carrying
capacity of the blood) → being oxidized → metHbg/
presence of methbg in the blood
Vit B12 → source for the vitamin deficiency
ACIDS AND BASES

• BASES- LIQUEFACTION NECROSIS

• ACIDS - COAGULATION NECROSIS

• TREATMENT: DILUTIONAL THERAPY

Excessive exposure to bases/Bases toxicity → commonly will cause liquefaction necrosis

Dilutional therapy →e.g. excessive bases → neutralization with acid and vice versa

Bases

• Alkaline ingestions cause tissue injury by liquefactive necrosis (TISSUEDEATH / CELL DEATH)
(saponification of fats and solubilization of proteins).The hydroxide ion of the base reacts with
tissue collagen and causes it to swell and shorten small vessel thrombosis and heat production
occurs.
• Ingestion of strong bases (alkali) can cause thick and slimy vomitus that may contain blood.
NECROSIS is the death or cell death because of the exposure to hydroxide ion = causing swelling and shortening
of tissues

Acids

• Acid ingestion causes tissue injury by coagulation-type necrosis (desiccation or denaturation of

superficial tissue proteins). This typically creates an eschar (dry scab) which tends to self-limit
further damage.
• Acid ingestion can cause a black bloody diarrhea, epigastric pain & esophageal strictures (5-20%)
- a narrowing or tightening of the esophagus making it difficult to swallow.
Result also cell death or necrosis but with different presentation only
Symptoms: eschar, black bloody diarrhea, epigastric pain and esophageal strictures

PHENOL

• CARBOLIC ACID

• STANDARD ANTISEPTIC

- derivative: Lysol (50% cresol)

- protein denaturant

• Phenol Coefficient→ basis of antibacterial action

- A: Dermal Exposure: PEG; Inhalation: 100% humidified Oxygen; Oral: Castor Oil, Mineral oil
Also called as carbolic acid
Standard antiseptic → in the times of Joseph Lister (discovered phenol) → where antibiotics are not yet
developed; high phenol coefficient = high antibacterial activity
The antibacterial → the antibacterial activity is attributed by its ability to denature the protein → CHON
denaturant
ANTIDOTE for dermal exposure: PEG
Cathartics → CO and MO

HOUSEHOLD TOXICOLOGY

HOUSEHOLD CHEMICAL ANTIDOTE

Ethylene Glycol Fomepizole, Ethanol
Methanol Ethanol and Fomepizole
Formaldehyde NH3 and NaHCO3
Acetone Neutralization with milk
Hydrocarbon Mineral Oil
Cyanide Amyl Nitrite, Na

Ethylene glycol → converting into oxalic acid → toxic in the kidneys

Methanol & Formaldehyde → formaldehyde (blindness/visual disturbances), formic acid (metabolic acidosis)
Metabolic acidosis → antidote: ammonium & sodium bicarbonate
Acetone → bcs it can cause CNS depression
HC from petroleum distillation
CN → can cause MetHgb

LEAD

MOT: combines with -SH (thiol group) -> inactivation of enzymes

-CANNED GOODS, AUTOMOBILE EXHAUST, WINE GLASSES, OLD PIPES, CABLES, PAINTS

-OLDEST OCCUPATIONAL POISON

Plumbism (BRAIN)

o Milky vomitus
o Black stool
o Wrist Drop/ Foot Drop
o Black Line gums / BURTON LINE (BURTONIAN LINE) → BLACK

-BLUE LINE VISIBLE ALONG THE MARGIN OF GUMS

A: BAL and CaNaZEDTA

Industrial → industries e.g. manufacturies, industrial pharmacy → exposed to certain metals

Binding of metal + -SH group = inactivation of enzyme (has a role in the key processes of the body) →
disturbances in the normal functions of the body
Present in canned goods, etc
Oldest occupational poison
Organ that is most affected: BRAIN → causing:
Black line gums/burton line or burtonian line → black to blue lines visible along the margin of the gums
Antidote: BAL & Calcium disodium EDTA
PLUMBISM

✓ ABDOMINAL PAIN
✓ CONSTIPATION
✓ HEADACHES
✓ IRRITABILITY
✓ MEMORY PROBLEMS
✓ INFERTILITY
✓ TINGLING SENSATION
Common signs and symptoms:
Memory problems → because brain is affected

CADMIUM

• Component of STINK BOMBS, Antidandruff shampoo

(CAPSEBON -> 1 % SUSPENSION OF CADMIUM SULFIDE)

• Itai -itai Disease (KIDNEYS, LUNGS AND BONES)

*Osteomalacia

*Fractures, Gaits and renal abnormalities

A: EDTA

Capsebon → containing 1% of cadmium sulfide → antidandruff shampoo

Osteomalacia → abnormality in the bones
Commonly affected organs: kidneys, lungs, and bones
INDUSTRIAL TOXICOLOGY

MERCURY / QUICK SILVER, LIQUID SILVER, NOBLE METAL

• MOT: Blockage of sulfhydryl group

• MINAMATA DISEASE:

-ACRODYNIA

o Pink palms and toes

o Oliguria

A: Na formaldehyde sulfoxinate and BAL

PENICILLAMINE

T: KI →(+) Orange

Reinsch→(+) Silver
Blockage of –SH group → causing prevention of cellular respiration → hypoxia
Common manifestation: Minamata disease → has the ACRODYNIA characteristics: pink palms and toes, oliguria
(dec. in the volume of urine/ low urine output)
Antidotes: best → Na formaldehyde sulfoxinate; BAL; and PENICILLAMINE (although → common used in Cu
toxicity)

ARSENIC

• Lewisite metal (SALVARSAN, CMPD 606, MAGIC BULLET - TREATMENT OF SYPHILIS)

• Protoplasmic poison
• Choice of professional poisoners
• FOUND IN FOWLER'S SOLUTION AND DONOVAN'S SOLUTION
o ALDRICH MEES' LINE / LEUKONYCHIA
o GARLIC ODOR BREATH
o LUMINOUS VOMITUS
o BLACK LINE GUMS

A: BAL

T: Marsh > (+) mirror-like↓

Reinsch> (+) dull black

AKA lewisite → used in the treatment of syphilis

Protoplasmic poison → toxic to the cell
Characteristics:
1. Aldrich mees’ line/ leukonychia striata → white lines of discoloration across the nails of the fingers and
toes
2. Black line gums → like lead but lead black-blue line while in arsenic → BLACK LINE
Reinsch → also in Mercury (+ silver) → in arsenic (+ dull black)

INDUSTRIAL TOXICOLOGY

IRON
• I - nausea, vomiting, diarrhea, Gl bleeding, hypotension
• II - clinical improvement seen 6-24 hours postingestion
• III - metabolic acidosis, renal & hepatic failure, sepsis, pulmonary edema, & death
A: DEFEROXAMINE

ORGANOPHOSPHATES
• Parathion and Malathion
• MOA: binds to AChE forming a stable phosphate-ester bond → inactivation of ACHE = 1
ACH (irreversible without treatment)
• D-iarrhea, diaphoresis
• U-rination
• M-iosis
• B-radycardia, broncoconstriction
 • E-mesis, excitation
• L-acrimation
• S-alivation
A: ATROPINE/ PRALIDOXIME

S. pilosus
Para and Mala → cholinergic insecticides
Diaphoresis → excessive sweating

STRYCHNINE
- MOA: blocks glycine (negative neurotransmitter) → seizures
• RIGOR MORTIS
• SPINAL CONVULSIONS
• SARDONIC SMILE
A: Diazepam, Phenobarbital, Neuromuscular blockers

PHOSPORUS
• LUMINOUS VOMITUS
• GARLIC ODOR OF BREATH
• LOOSE TEETH
A: CuSO4 T: Mitschelich → (+) phosphorescene
Scherer → (+) Black
MOA: inhibit glycine
GLYCINE’S ROLE: inhibit other NT → x inhibitory = increase in the amount of NT → causing seizures
DZM & Pheno for seizures, neuromuscular blockers for rigor mortis

ALUMINUM
- causes SHAVER'S DISEASE
- 3rd most abundant element & most abundant metal on earth
- has CONSTIPATING & astringent effects

ZINC
- Def: Parakeratosis
• used in the galvanizing of iron & container for battery cells
• deficiency: Parakeratosis (thick, inflamed, scaly skin)
• toxicity: Metal Fume Fever (muscle aches & fever)
• treatment: Aspirin + bed rest (recovery occurs after 1-2 days)
A: ASA

Ala Tae → constipation

Mg Tae → diarrhea

ASA → analgesic and antipyretics

CC14
- non-flammable cleaning fluids & fire extinguishers
- Metabolite: PHOSGENE
- T: Nessler + Yellow ppt

СО
- exhibits 210x more affinity to Hgb compared to oxygen
- TOX: METHEMOGLOBINEMIA
- A: HYPERBARIC 02
Carbon tetraCl
MetHgb → oxidized form of oxygen

KI → (+) Orange
Reinsch → (+) Silver
Marsh → (+) mirror-like
Reinsch → (+) dull black
Mitschelich → (+) phosphorescene
Scherer → (+) Black
Nessler → Yellow ppt
Liben's Iodoform – yellow popt.
Picrate test → (Yellow)
Schonbien-Pagenstecher – (+) Deep blue
Benzoldt Gunning → (+) indigotine

QUIZ
1. A metal that causes shaver's disease.
2. A metal that causes Itai-itai disease.
3. Blue-black lining of the gums is also known as
4. A metal that causes parakeratosis.
5. A metal that causes Aldrich mees line,
6. It gives yellow ppt. in Lieben's lodoform.
7. Acid ingestion causes tissue injury by
8. It contains 50% cresol.
9. Benzoldt Gunning is a test for
10. An enzyme responsible for the conversion of Methanol to formaldehyde.
11. Antidote for Copper toxicity
12. Solvent for BAL
13. Route of administration of Unithiol
14. Other name of Penicillamine.
15. Garlic odor breathe
16. It can cause dyspnea.
17. Final toxic metabolite of ethylene glycol.
18. Antidote for organophosphate poisoning
 19. Give examples of cathartics.
20. Reinsch test, + silver.
21. Reinsch test, + dull black.
22. It can cause excessive sneezing.
23. Toxin associated with rigor mortis
24. The hydroxide ion of the base reacts with tissue collagen and causes it to swell and
shorten
25. Blue black lining of gums is also known as
26. Zinc toxicity.
27. Antidote for Zn toxicity
28. Parent drug of phosgene
29. Found in the form of “canned heat” or in windshield washing products
30. It may cause acrodynia.

SUBSTANCES FOR ABUSE

SCHEDULE OF DRUGS
I high potential for abuse and no accepted Flunitrazepam medical use
All illegal under law Narcotics: Heroin
Hallucinogens: LSD,
Mescaline PCP,
Psilocybin
II high potential for abuse, but do have a Opiods: Morphine,
currently accepted medical use in treatment Codeine
No telephone prescription Stimulants: Amphetamine BB
No refills (Amo, Pento, Seco)
III have accepted medical use in the US, but they Ketamine, Dronabinol,
have a lower potential for abuse than Schedule Anabolic steroids
I and II drugs Prescription must be rewritten
after 6 months or five refills
IV lower potential for abuse than Schedule III Pentazocine
Prescription must be rewritten after 6 months BZD
or five refills Phenobarbital
V the lowest abuse potential of the controlled Diphenoxylate
substances Dihydrocodeine
OTC Preparations
Nonopioid prescription drugs

Schedule 2 → has medical uses → x illegal

Diphenoxylate → antidiarrheal
Dihydrocodeine → antitussive
 SUBSTANCES OF ABUSE TREATMENT
1. AMPHETAMINE/ Attention Deficit Hypereactivity Disorder
METHAMPHETAMINE (ADHD) A: CNS DEPRESSANTS
2. OPIOIDS Natural: opium, morphine A: NALOXONE, Naltrexone, Nalorphine,
Semi-synthetic: heroin & codeine Nalmefen
Synthetic: methadone & meperidine

Amphetamine → CNS stimulant

Heroin- a.k.a“ diamorphine”, “diacetylmorphine

Codeine- 2nd most abundant in opoiod.
3-methylmorphine-- Synthetic congener of codeine is DEXTROMETHORPHAN
Methadone- doc for opoiod withdrawal
Meperidine- Shortest duration of analgesia, Preferred for analgesia during labor

MARQUI’S TEST TEST FOR METAM/AMPHE, ECSTASY,

- dark purple/black (Ecstacy), PROPOXYPHENE, HEROIN, OPIATES,
- orange to brown (Amphetamine & Methamphetamine) ASA
- purple/black (Propoxyphene)
- pink to purple (Heroin & Opiates)
- red (Aspirin)

Nalbuphine K-receptor agonist Nubain

Mu receptor antagonist
Naloxone Mu antagonist Narcan
Shortest duration of action IV
Naltrexone Oral administration Tx of Trexan, Revia
constipation
Nalmefene Newest agent derivative Revex
Longer half life

SUBSTANCE OF ABUSE
SEDATIVES TREATMENT
1. BENZODIAZEPINES + alcohol → fatal CNS & respiratory
depression
A: Flumazenil (Mazicon ®)
2. BARBITURATES used for induction of anesthesia & for
seizures Cheyne-Stokes (irregular) respiration
 A: Forced alkaline diuresis, hemodialysis
3. . CHLORAL HYDRATE MICKEY FINN
in vivo via alcohol dehydrogenase →
Trichloroethanol
A: SUPPORTIVE

Barbi → used for induction of anesthesia and seizures esp. thiopental

Antidote: supportive treatment
Active metabolite → trichloroethanol; toxic metabolite → trichloroacetic acid

ABUSE HALLUCINOGENS KEY NOTE!

1. LSD MOA: inhibits serotoninergic firing →
sympathetic stimulation and
hallucinations
treatment: Benzodiazepines for seizures
2. MESCALINE peyote cactus (Lophophora williamsii)
- "BUTTONS"
3. ECSTACY MDMA
(methylenedioxymethamphetamine)
- MOA: serves as a false neurotransmitter
→ release of catecholamines & inhibition
of MAO, also stimulates B & a receptors Common name: buttons
(similar to amphetamine) LSD → can cause
seizures
- Toxic dose: 50-150 mg - treatment: Stimulates →
Labetalol, Nitroprusside, or Nifedipine for catecholamines such as
HPN NE and Eph, Dop; and
4. PHENCYCLIDINE - dissociative anesthetic, "angel dust" - inhibit → MAO
(metabolism of
signs & symptoms: coma, acute brain
catecholamines NE, Eph
syndrome (disorientation, psychosis, = increase NT) = Causing
coma) now HTN & tachycardia
- treatment: Diazepam for seizures, (inc. HR)
Nitroprusside for HPN 4

MARIJUANA
✓- Cannabis sativa
✓ - most commonly used illegal drug
✓ - hashish or hash oil
✓ - active ingredient: tetrahydrocannabinol (THC)

COCAINE
✓ - Erythroxylon coca, crack, freebase
✓- CNS & sympathetic stimulation
✓- treatment:
Benzodiazepines: seizures
Labetalol: HPN
Neuroleptics: psychosis
Hashish or hash oil → cannabis oil; STREET NAME: Mary Jane
Cocaine → mostly used as anesthetic drug → not use now → because: CNS & sympathetic stimulation =
rapid HR

ETHANOL
• grain alcohol, neutral spirit
• responsible for major medical & socio-economic problems
• alcohol content:
o beer: 4 -5%
o wine: 10 - 14%
o distilled spirits:
• (whiskey, vodka, rum, brandy): 30 - 50%
• metabolites: acetaldehyde, acetic acid
• signs & symptoms:CNS depression, acid-base imbalance,
• impaired thermal regulation, hypoglycemia
• treatment:
o Thiamine (prevention of Wernicke-Korsakoff syndrome)
o Disulfiram (Antabuse ®) (used to stop alcohol addiction)
Alcohol intoxication → Wernicke Korsakoff syndrome → affects the metabolism of thiamine → antidote:
administration of thiamine/Vit B1 such as peanuts → peanut is a good source of thiamine/Vit B1 (e.g.
inuman → pulutan → peanuts wais)

NICOTINE -Nicotiana tabacum

✓ - active ingredient of tobacco for the addictive effect
✓ - lethal dose:
o adults: 40 - 60 mg
o child: 1.5-2 mg/kg V
✓ treatment: activated charcoal, gastric lavage

NITROUS OXIDE
✓ - laughing gas
✓- may cause diffusional hypoxia
✓ - hysterical laughing
✓- treatment: Oxygen

TERMS!!!
• MUTAGENESIS
- heritable changes in genetic material that are limited to the effects on the nucleic acid
 • HAPTENS
- chemicals with molecular weights of less than 1000 and generally react with
endogenous carrier molecules to become antigens before they exhibit immunogenicity.

• CLASTOGENESIS
- chromosomal breakage resulting in rearrangement of pieces of chromosomes
Mutagens → substance causing mutagenesis
Haptens → must firstly attach to a carrier molecule → before it can be an immunogen (antigen that
produces immunity)

Clinical Toxicology

WARFARIN
- MOA: inhibition of vitamin K-related clotting factors (II, VII,IX,X) principal manifestation:
bleeding
- Tx:Vitamin K1

HEPARIN
- principal manifestation: bleeding
- treatment: Protamine sulfate - acts as the base to neutralize heparin acidity (1mg
Protamine = 100IU Heparin)

SALICYLATES
• signs & symptoms:
• mild: tinnitus, malaise
• severe: lethargy, convulsions, coma, metabolic acidosis
• treatment:
o Urine alkalinization with NaHCO,
o Vitamin K / fresh frozen plasma for bleeding
o Hemodialysis or hemoperfusion (> 100 mg/dL)

ACETAMINOPHEN
• I: anorexia, diaphoresis
• II: asymptomatic
• III: abdominal pain, hepatic failure, coma, death
• treatment: N-Acetylcysteine (NAC) (PO) - acts as a precursor for glutathione

CHLORAMPHENICOL
- Gray baby syndrome: Gl disturbances, vomiting, anorexia, abdominal distention,
diarrhea, hypothermia, hypotension, & cyanosis .
- Aplastic anemia (idiosyncratic), bone marrow depression
- treatment: charcoal hemoperfusion
NaHCO3 → to neutralize the acidity
Signs and symptoms of acetaminophen → I, II, III
Accumulation of chloramphenicol → Gray baby syndrome or bilirubinemia

VANCOMYCIN
• Red man neck syndrome

DIGOXIN
- TX:Lidocaine/Phenytoin
- Digoxin:specific Fab antibodies
- Potassium chloride

Visual Disturbances Substance/s

Purple vision Digitalis, marijuana
Blurred vision Anti-cholinergics
Partial/ total blindness Methanol, formic acid, solanine
Optic neuritis Ethambutol
Blood shot eyes Marijuana

MUSCLE RELAXANTS
• Succinylcholine and Tubocurarine
• MALIGNANT Hyperthermia-Succinylcholine
• Histamine release - Tubocurarine
• Tx:Epinephrine, dantrolene ,neo/pyridostigmine

METHYLXANTHINE
• Theophylline
• Seizures, Cardiac arrythmias
• Tx:Ipecac syrup, Activated Hemodialysis,B blocker

LITHIUM CARBONATE
• DOC: MANIA or BIPOLAR DISORDER
• Tx :Ipecac, Na polystyrene sulfinate, WBI(SR) WBI – Whole Bowel Irrigation
• Hemodialysis(rebound effect)

TCA's
• Anticholinergic signs and symptoms
• Cardiopulmonary toxicity
• CNS manifestations
• TX:NAHCO3,Phenytoin,BZD, Physostigmine

ISONIAZID
• hepatitis, peripheral neuropathy
 • TX:Vitamin B6 (pyridoxine)

BETA BLOCKERS
• Hypotension, Avblock, Bradycardia(Bronchospasm)
• Tx:Glucagon, Epinephrine

CALCIUM CHANNEL BLOCKERS

• hypotension
• Tx: Glucagon
POTASSIUM
• Cardiac irritability, dysarrythmias,peripheral weakness
• Tx: Calcium Chloride-hyperkalemia

Odor of Breath Substance/s

Shoepolish Nitrobenzene
Fruity odor Ethanol
Garlic Arsenic, phosphorus, malathion, thallium
Mouse urine Coniine
Stake tobacco Nicotine
Bitter almonds Cyanide
Sweet, penetrating odor Acetone, chloroform
Pearlike Chloral hydrate
Rotten egg Hydrogen sulphide
Mothballs Naphthalene
Wintergreen Methylsalicylate

Skin Discoloration Substance/s

Yellow Picric acid, nitric acid
Bleaching white Phenol
Ash gray Mercuric chloride, physostigmine
Deep brown Bromine
Brown black Sulphuric acid, iodine, AgNO3
Bluish gray Silver salts
Blue Cyanotics (opium, aniline, sulphides
Pale bonds on fingermails Arsenic
Boiled lobster appearance Boric acid
 LEGAL PHARMACY AND ETHICS

JURISPRUDENCE  is defined as a system of laws ETHICS  is the science of morality

• is the science of philosophy of laws  It refers to the moral principles of practice
 Latin: Juris Prudencia (study of law)  Greek: Ethos (customs, habit, character)
 The same set of systems/law = general  What is GOOD for individual & society and the
moral philosophy
• MORALIT  Varied per individual (beliefs,
perceived)

IMPORTANCE OF JURISPRUDENCE IN THE PHARMACY PRACTICE: for decision making as well as the actions
concern which is consistent with the current clinical principles in the practice, protect the pharmacists from liability
 hence should be familiar with the laws and legal requirements in the practice of pharmacy

THREE TYPES OF LAW SYSTEM

1. STATUTORY LAW created for the proper bureau circular  passed
 Passed by the Senate or the regulation and by the FDA
Congress implementation of the
 Dictate the activities of the former law COMMON LAW
person  Promulgated by the  Principle: STARE DECISIS -
 Provide penalties for those government agencies (FDA) the policy of courts to stand
who do not comply  For the reinforcement and by precedent
 Ex: Republic Acts (RA) understanding of the  Allowing the state to decide
law/support the statutory  Covers the areas of the law
2. REGULATORY LAW laws that have evolve over
 Supports the Statutory law  Ex: administrative order, hundreds judicial decisions
wherein this has been memorandum, circular,

UNIVERSAL PRINCIPLES OF BIOMEDICAL ETHICS

 AUTONOMY allow patient to choose (e.g. generic vs. branded) and respect
 VERACITY tell the truth/be honest
 BENEFICENCE do good, promote common good
 NONMELEFICENCE do no harm  x drugs to injure someone  wrong/cause disease
 CONFIDENTIALITY prevent privilege information release/protect confidentiality of the patient
 JUSTICE fairness
 ROLE FIDELITY faithfulness  practice faithfully within the areas of the law

RA TITLE DATE
RA 5921 PHARMACY LAW (Old law)  standardization & regulation of JUNE 23,1969
pharmacy education, board examination, & practice of pharmacy
RA3720 FOOD, DRUG, DEVICES AND COSMETICS ACT JUNE 22, 1963
RA 6675 GENERICS ACT SEPTEMBER 13, 1988
RA 7432 SENIOR CITIZEN ACT OF 1992 APRIL 23, 1992
RA 9257 EXPANDED SENIOR CITIZEN ACT OF 2003 FEBRUARY 26, 2004
RA 9994 EXPANDED SENIOR CITIZEN ACT OF 2010 FEBRUARY 15, 2010
RA 9165 COMPREHENSIVE DANGEROUS DRUG ACT OF 2002 JUNE 7,2002
RA 6425 DANGEROUS DRUG ACT OF 1972 APRIL 4, 1972
RA 8423 TRADITIONAL AND ALTERNATIVE MEDICINE (TAMA) 1997 DECEMBER 9,1997
RA 8203 SPECIAL LAW ON COUNTERFEIT DRUGS JULY 22, 1996
RA 7394 CONSUMER'S ACT APRIL 13, 1994
RA 7581 THE PRICE ACT MAY 7, 1992
RA 9502 UNIVERSALLY ACCESSIBLE CHEAPER AND QUALITY MEDICINES ACT OF JUNE 6, 2008
2008
RA 9711 FDA ACT OF 2009 AUGUST 18,2009

R.A. No. 10918 The Philippine Pharmacy Law (New Pharmacy law)  start as Health Bill 5616 implement on May
23, 2016 Senate bill 2436 on May 30, 2016  x signed by the former president Aquino but because of the
transition of power = automatic
 An act Regulating and Modernizing the Practice of Pharmacy in the Philippines, repealing for the purpose
Republic act number five thousand nine hundred twenty-one (R.A. No. 5921), otherwise known as the
Pharmacy Law Signed into law on July 21, 2016
 Update on the regulation and practice of pharmacy in the Philippines (modernization)

ARTICLE I GENERAL PROVISIONS

SECTION 3 OBJECTIVES
This act provides for and shall govern the
 Standardization and regulation of pharmacy education
 Administration of licensure examination, registration and licensing of Pharmacists
 Supervision, control, and regulation of the practice of pharmacy in the Philippines
 Development and enhancement of professional competence of pharmacists through continuing
professional development, research, and other related activities
 Integration of the pharmacy profession

SCOPE OF THE PRACTICE OF PHARMACY (MUST ABIDE w/  Philippine Practice Standard for Pharmacist which
provide set of principle guidance in the practice of pharmacy, GMPs and GCP  vital in the performance of
pharmacist’s role and function in different practice areas)
Article 1 Section 4
 Compounding  Vaccine Administration  immunizing RPh
 Dispensing and Counselling  pharmacist being involved in the
 Teaching administration (aside from storage and
 Physico-chemical, Biological Microbiological dispensing functions)
Analyses  Research

QUALIFICATIONS of the Chairperson and Members of the Board (licensure examination) Article II, section 7
 APPOINTED BY THE PRESIDENT
 Term of Office: 3 years, **May be reappointed for another term Article II, section 9

CHAIRPERSON
 Not affiliated in any school, review center or  Have not been convicted of a crime
similar institution  RPh or MS degree holder
 At least 5 yrs membership in APO (Accredited  10 yrs experience  within pharmacy areas
Professional Organization e.g. PPhA  Filipino citizen

MEMBERS OF THE BOARD OF PHARMACY

Chairperson Hon. MILDRED OLIVEROS (serves as 3-6yrs  appointed by the president)
First member Hon. ANTHONY ALDRIN SANTIAGO (2-4yrs)
Second memberHon. ADELINA ROYO (1-2yrs)
In case of VIOLATIONS: Suspended NMT 60days, INCOMPETENCIES/IMMORALITY/CRIMES  removal

QUALIFICATIONS FOR THE LICENSURE (Article III, section 14)

Applicant for the Pharmacist Licensure Examination
 Filipino citizen or of a foreign country which has a law or policy on reciprocity or the practice of the
pharmacy profession
  Of good moral character and reputation
 Degree holder of Bachelor of Science in Pharmacy
 Has completed an internship program (community, hospital, industry/manufacturing, institution, public
health/regulatory)

SCOPE OF EXAMINATION Article III, section 15

 Inorganic Pharmaceutical Chemistry,  Quality Assurance and Instrumentation
 Organic Pharmaceutical Chemistry,  Pharmaceutical Calculations,
 Qualitative and Quantitative  Drug Delivery Systems,
Pharmaceutical Chemistry, Pharmacognosy  Hospital Pharmacy,
and Plant Chemistry,  Clinical Pharmacy,
 Pharmaceutical Biochemistry,  Dispensing and Medication Counseling
 Microbiology and Parasitology,  Pharmaceutical Administration and
 Physical Pharmacy,  Management,
 Biopharmaceutics,  Public Health,
 Pharmacology and Toxicology,  Legal Pharmacy, and Ethics
 Manufacturing,

Module 1: CHEMISTRY
Module 2: Pharmacognosy, Biochemistry
Module 3: Dispensing, Hospi, Clinical, PCAL
Module 4: BP, PCOL 1/2, Clinical toxicology
Module 5: DDS, Manuf, Cosmetics, Jurisprudence, Physical pharmacy
Module 6: QC, QA, Microbiology, Public health

Article III, section 17

 In order to be registered and licensed as a pharmacist, a candidate must obtain a general weighted average
of seventy-five percent (75%), with no rating lower than fifty percent (50%) in any of the subjects.
 An applicant who failed in the licensure examination for the third (3rd) time shall not be allowed to take the
next succeeding examinations without having undertaken a refresher program (REFRESHER 
implemented by PACOP/Philippine Association of the COP  certification) in a duly accredited institution.
The Board shall issue guidelines on the refresher program requirement.

Article III, section 16

• The Pharmacist Licensure Examination shall be given two (2) times (March or April/ September or October) a
year in places and dates as the PC may designate in the Resolution providing for the master schedule of all
licensure examinations pursuant to Section 7(d) of Republic Act No. 8981.

SUCCESSFUL candidates in the licensure examination

 shall take their Oath of Profession (Article III, section 19)
 Will receive Certificate of Registration and Professional Identification Card (subject to compliance with
the registration requirements and payment of the prescribed fees.) (Article III, section 20)

PIC (Professional Identification Card) will include the following information:

 registration number,
 dates of its issuance and expiry,
 Signature of the Chairperson of the PRC
 issued to every registrant, upon payment of the prescribed fees.
 shall be renewed every three (3) years (expired for 3 years), upon presentation of the following:
Certificate of Good Standing (COGS) from the APO and proof of completion of the CPD requirements
st nd
(CPD-Continuing Professional Development) 1 time = No CPD units; 2 time = before 45 units, now
15 units)
 REGISTERED AND LICENSED Pharmacist
 have the right to affix to one's name, the "RPh". (Article /V, section 26)
 When employed he/she should display the original copy of one's COR in a prominent and conspicuous place
in the drug establishment (Article IV, section 29)
 The only one to fill, compound and dispense Prescription drugs and pharmacist-only OTC medicines (Article
IV, section 30 and section 33) ensure that all pharmaceutical products conform to standards of safety,
quality and efficacy, as provided for in this Act and other pertinent rules and regulations and issuances.
(Article IV, section 32)
 must be members of the APO (PPhA  1 time: HONORARY MEMBER  then renew membership) and
st

must maintain membership throughout the duration of the practice of the profession (Article V, section 42)

PHARMACIST REQUIREMENT (Article IV. Section 31)

Establishments/outlets which are required to employ and/or retain and maintain the professional services of duly
registered and licensed pharmacists shall be classified as follows:

Category A  Pharmaceutical establishments/outlets where the direct and Category B  Pharmaceutical establishments/outlets
immediate control and supervision of a duly registered and licensed pharmacist is where the supervision and oversight of a duly
required, per establishment, whether in-store or online registered and licensed pharmacist is required under
pertinent provisions of law.
(1) Pharmaceutical establishments/outlets selling or otherwise making available to (1) Retail outlets selling household remedies and
the consuming public prescription/ethical medicines, combination products OTC drugs as differentiated from the pharmacist-
(medical device and drugs) classified as drugs according to the primary intended only OTC medicines;
mode of action, pharmacist-only OTC medicine, whether owned by the government (2) Satellite institutional pharmacies providing
or by a private person or firm, whether sold at wholesale or retail; medicines solely to employees of their respective
(2) Establishments involved in the manufacture, importation, exportation, companies or the employees' qualified dependents,
distribution, and sale of combination products (medical device and drugs) classified or both; or members of a duly registered
as drugs according to the primary intended mode of action; organization or institution;
(3) Departments/Divisions/Units of pharmaceutical laboratories, pharmaceutical (3) Fourth, fifth and sixth class municipal health units
manufacturing laboratories, or other establishments with processes involving the involved in the procurement, distribution, dispensing,
preparation, manufacture, assay, regulation, product research and development, and storage of pharmaceutical products;
quality control, repacking, importation, exportation, distribution, sale or transfer of (4) Institutions providing telepharmacy services; and
pharmaceutical products in quantities greatly in excess of single therapeutic doses; (5) Non-traditional outlets of pharmaceutical
(4) Government units, including local government, city, first to third class municipal products: Provided, that no prescription medicines
health units, nongovernment organizations and/or associations involved in the and pharmacist-only OTC medicines are sold.
procurement, distribution, dispensing and storage of pharmaceutical products;

PHARMACIST REQUIREMENT (Article IV, section 31)  x 1:1 RPh ratio per pharmacy esp. if CLASS B
A pharmacist working in a Category A establishment may be allowed to simultaneously work or render pharmacy
services in Category B establishments, the maximum number of hours of which shall be determined, in
accordance with such guidelines as may be established therefore by the Board, in coordination with the FDA, and
other agencies, establishments, institutions, and regulatory bodies.

ARTICLE V  Accredited Professional Organization

Section 41. A pharmacist duly registered with the Board shall automatically become a member of the integrated
and accredited professional organization of pharmacists, and shall receive the benefits and privileges
appurtenant thereto upon payment of the required fees and dues.

ARTICLE VI  Violations, Administrative Sanctions, and Procedures

The Board (BOP) shall have the power, upon notice and hearing, to revoke or suspend the COR of a registered
pharmacist or to cancel an STP (special temporary permit) of a foreign pharmacist on any of the following grounds:
(a) Violation on the policies and regulations in the practice of pharmacy
(b) Conviction of an offense involving moral turpitude by a court of competent jurisdiction (e.g. jail time);
(c) Unprofessionalism, immorality, malpractice, incompetence, gross negligence, or imprudence in the practice of
the profession;
(d) Fraud or deceit in the acquisition of the COR, PIC or STP, or renewal thereof;
(e) Allowing the COR to be used or displayed in establishments where the pharmacist is not actually employed and
practicing  ghost pharmacist;
(f) Addiction to alcoholic beverages or to any habit-forming drug rendering a pharmacist incompetent to practice
the profession as provided for in Section 23 thereof;
(g) Aiding or abetting the illegal practice of a non-registered and licensed person;
(h) Insanity or any mental disorder that would render the person incompetent to practice pharmacy;
(I) False, extravagant, or unethical advertisements and endorsements of pharmaceutical products, pharmaceutical
outlets and establishments where the pharmacist's name or the pharmacist's professional organization and similar
information, or both, are used;
(J) Manufacture, sale, offering for sale of counterfeit, spurious, substandard and falsified pharmaceutical products
and committing other acts in violation of Republic Act No. 9165 and Republic Act No. 8203, otherwise known as
the "Special Law on Counterfeit Drugs":
(k) Illegal manufacture, sale, possession, dispensing of dangerous drugs and other acts in violation of Republic Act
No. 9165, and other applicable laws and issuances;
(I) Committing acts in violation of Section 6 of Presidential Decree No. 881, entitled "Empowering the Secretary of
Health to Regulate the Labeling, Sale and Distribution of Hazardous Substances" and Section 11 of Republic Act No.
3720, as amended;
(m) Practicing pharmacy with a suspended COR or expired PIC;
(n) Unauthorized dispensing of pharmaceutical products through unregistered online services or direct selling
businesses;
(o) Being found guilty of immoral, unprofessional, or dishonorable conduct by the Board

ARTICLE VII  Penal Provisions

Any person who shall commit any of the acts stated in this section, upon conviction, be sentenced
• to pay a fine of not less than two hundred fifty thousand pesos (P250.000.00), but not exceeding five
hundred thousand pesos (P500.000.00)  250K – 500K
• or imprisonment of not less than one (1) year and one (1) day but not more than six (6) years, or both, at the
discretion of the court.  1 year and 1 day – 6 years

WHAT ARE THESE GROUNDS?

 Commission of any act in violation of Sections 30 and 31 of this Act;
 Allowing the display of one’s COR in a pharmaceutical establishment where the pharmacist is not employed
and practicing
 Dispensing or allowing the dispensing or offering for sale of prescription drugs where the outlet is not
registered with the FDA
 Dispensing of prescription and pharmacist-only OTC pharmaceutical products by a person other than those
under the direct and immediate supervision of a duly registered and licensed pharmacist

OTHER PENALTIES
• to pay a fine of not less than one hundred thousand pesos (P100,000.00), but not exceeding two hundred
thousand pesos (P200,000.00)
• or imprisonment of not less than thirty (30) days but not more than one (1) year, or both, at the discretion of
the court
The owner/operator of the pharmaceutical establishments/outlets and the duly registered and licensed
pharmacists/pharmacy support personnel are jointly liable for the willful violation of any provision of this Act.
Republic Act No. 3720 (Food Drug and Cosmetics Act)  (As amended by E.O. No. 175, May 22, 1987) 
approved June 22, 1963 but amended to law on May 22, 1987 by EO 175 (TO INCLUDE THE DEVICES = hence, FDDC
Act)
 "An act to ensure the safety and purity of foods and cosmetics, and the purity, safety, efficacy and quality
of drugs and devices being made available to the public, vesting the Bureau of Food and Drugs (BFAD  FDA)
with authority to administer and enforce the laws pertaining thereto, and for other purposes."

DECLARATION OF POLICIES  Section 3: The government shall:

 Establish standards and quality measures (FDDC) (food drug devices and cosmetics)
 Adopt measures to ensure pure and safe supply of FDDC
 Adopt measures to ensure the rational use (of FDDC) such as banning, recalling or withdrawing – also
adoption of an official National Drug Formulary – use of generic names in labels
 Strengthen the Bureau of Food and Drugs (FDA)

CREATION OF THE FOOD AND DRUG ADMINISTRATION

 Created to carry out provision of this act
 It is an office inside the Department of Health
 It shall be under the Secretary of Health

POWERS, DUTIES, RESPONSIBILITIES (FDA)  Section 4

1. To administer and supervise the implementation of this Act and of rules and regulations
2. To provide for the collection of samples of FDDC
3. To analyze and inspect FDDC
4. To establish analytical data to serve as basis for the preparation of FDDC standards - and recommend standards
of identity, purity, quality and fill of container.
5. To issue certificate of compliance
6. To collect fees for inspection, analysis and testing of products and materials
7. To certify batches of antibiotic and antibiotic preparations

DIVISIONS  Section 5 (Amended by RA 9711 the DIVISIONS of FDA divided by 2:

(1) Inspection and Licensing Division- responsible in regulate drug establishment, distributor, manufacturing
(2) Laboratory Division - who inspect food, drug, devices and cosmetics available in market

FDA HAVE CENTERS AND OFFICES (centers that establish MAJOR PRODUCT CATEGORY)
 Center for drug regulation and research (including veterinary medicines, vaccines, biologicals)
 Center for food regulation and research
 Center for cosmetic regulation and research (including household hazardous chemicals, urban substances)
 Center for device regulation, radiation health and research
 These centers regulate the manufacture and exportation and distribution sale of these FDDC products and
organize by which it should have the following:
(1) Each centers are headed by a DIRECTOR
(2) DIVISIONS (Inspection and Licensing Division – responsible for the evaluation of health products of
establishments and Laboratory Division – responsible for the conduct of research, appropriate tests,
calibration analysis, trials of the products, conduct oversight and audit for centers conducting the BA & BE,
and other pertinent tests)

HEAD  Section 6
 FDA administrator (Undersecretary Rolando Enrique Domingo, DPBO OIC  Diplomate, Phil under the Board
of Otolaryngology, Director General)
o Head
o Appointed by the Secretary of Health
Section 7: Secretary may add more personnel as may be needed

PROHIBITED ACTS AND PENALTIES  Section 11:

1. Manufacture, importation, exportation, sale, offering for sale, distribution or transfer of any food, drug, device
or cosmetic that is adulterated or misbranded.
2. The adulteration (-addition of other substances, being inferior to the quality) or misbranding (-if the label is
false or misleading/exaggerated e.g. Vit C’s claim instead of antioxidant  ANTICA) of any food, drug, device, or
cosmetic.
3. The refusal to permit entry or inspection as authorized by Section twenty-seven hereof or to allow samples to
be collected.
4. The giving of a guaranty or undertaking which is false
5. Forging (-imitation), counterfeiting, simulating, or falsely representing or without proper authority using any
mark, stamp tag, label, or other identification device
6. Revealing information which is a trade secret
7. The alteration, mutilation (-cause of harm/injury/ serious damage), destruction, obliteration, or removal of the
whole or any part of the labeling of, the doing of any other act with respect to, a food drug, device, or cosmetic
8. The use of any representations in suggesting an application which is false (in labeling and advertisement
9. Use of report of analysis from FDA without authorization
10. The manufacture, importation, exportation, sale, offering for sale, distribution, or transfer of any drug or
device which is not registered with the FDA.
11. The Manufacture, importation, exportation, sale, offering for sale, distribution, or transfer of any drug or
device by any person without the license from the FDA
12. The sale or offering for sale of any drug or device beyond its expiration or expiry date.
13. The release for sale or distribution of a batch of drugs without batch certification

What are the penalties for violating any of the provisions of Section Eleven? RA 9711
= IMPRISONMENT of NLT 1 year but not more than 5 years & FINE of NLT 5K – NMT 10K (amended).

LICENSING AND REGISTRATION  Section 21

1. No person shall Manufacture, sell, offer for sale, import, export, distribute or transfer any drug or device
 Unless an application is filed for (License application) by the FDA

REQUIREMENT FOR THE APPLICATION UNDER OATH

- Investigations showing drug or device is safe, efficacious and of good quality (according to clinical trials
- Full list of the articles used as components
- Composition of such drug
- Description of the methods, facilities used for manufacture
- Drug samples
- Label specimen
- Other which would be required

CERTIFICATE OF DRUGS CONTAINING ANTIBIOTICS  Section 22

1. The Secretary provide for the certification of antibiotic
2. Whenever the requirements not necessary to ensure, safety and efficacy of use and good quality, the Secretary
shall promulgate regulations exempting such drug or class of drugs from such requirements.
3. Secretary shall promulgate regulations:
 drugs which are to be stored, processed, labeled, or repacked at establishments other than those where
manufactured, on condition that such drugs comply with all such requirements upon removal from such
establishments
 drugs which confirm to applicable standards of identity, strength, quality, and purity prescribed by these
regulations and are intended for use in manufacturing other drugs
  drugs which are intended for investigational use by experts qualified by scientific training and experience to
investigate the safety and efficacy of drug

ADULTERATED AND MISBRANDED COSMETICS  Section 23 and 24

1. If it contains poisonous or deleterious substance (EXCEPT HAIR DYES) if:
o It contains: "Caution: This product contains ingredient which may cause skin irritation on certain
individuals“
o It contains “This product must not be used for dyeing the eyelashes or eyebrows; to do so may cause
blindness”
 Others are same with FDD
 Misbranded cosmetics are also the same with FDD*

Adulterated - if have (1) poisonous/deleterious substances injury, (2) composed or imparted with filthy, putrid ,
decomposed, (3) packed under unsanitary condition,
Misbranded – if have (1) false or misleading label, (2) the label should contain = name, place
business/manufacturing, accurate quantity (weight, measure of numerical count) of the components provided
under reasonable variation shall be permitted and exemption as small packages established by regulation
prescribed by the secretary, (3) word, statement and other info missing on the label, (4) container is misleading

ADMINISTRATIVE SANCTIONS, REGULATIONS, HEARING, AND INSTITUTION OF CRIMINAL ACTION  Section 26

 Report products to the FDA
 FDA would conduct testing
 If the product is indeed adulterated, misbranded, not registered, the Director shall:
○ Give notice to the complained parties  general notice
○ Issue a hearing to impeach the correctness of the findings

ADMINISTRATIVE ORDERS/EXECUTIVE ORDER/MEMORANDIUM CIRCULAR:

AO 42 Drug Registration of Herbal and/or Traditional
AO 4 Availing of Compassionate Special Permit (CSP)
AO 27 Licensing Local Manufacturers Of Vaccines And Biologic Products
AO 55 Labelling Requirement
AO 56 Licensing to operate -UPDATED: AO 34
EO 302 Adopting PNDF as Immediate Reference of Standards
EO 119 Reorganizing BFAD
MC 15 Exemption from Requiring One Pharmacist Every Area
MC 17 Pharmacist Monitoring Hours
AO 62 Prescribing Requirement
AO 63 Dispensing Requirement
AO 67 Registration of Pharmaceutical Products

Food and Drug Administration FDA act of 2009 (RA 9711)

 An act strengthening and rationalizing the regulatory capacity of the Bureau of Food and Drugs (BFAD)
renaming it the Food and Drug Administration (FDA)
 Amended certain sections of RA 9720
 DATE OF APPROVAL: AUGUST 18, 2009

Section 1  A LAW THAT RENAMED THE BUREAU OF FOOD AND DRUGS (BFAD) TO FOOD AND DRUG
ADMINISTRATION (FDA).

Section 3  It is hereby declared a policy of the State to adopt, support, establish, institutionalize, improve and
maintain structures, processes, mechanisms and initiatives that are aimed, directed and designed to: (a) protect
and promote the right to health of the Filipino people; and (b) help establish and maintain an effective health
products regulatory system and undertake appropriate health manpower development and research, responsive
to the country’s health needs and problems. Pursuant to this policy, the State must enhance its regulatory capacity
and strengthen its capability with regard to the inspection, licensing and monitoring of establishments, and the
registration and monitoring of health products

Sections 4  OBJECTIVES:
 Enhance and strengthen the administrative and technical capacity
 Ensure the FDA’s monitoring and regulatory coverage
 Provide coherence in the FDA’s regulatory system

FUNCTIONS, POWERS AND DUTIES

 Implementation  verification of complaints
 collection of samples  establish analytical data
 analyze and inspect the health n safety of public  to prescribes standards, guidelines and
 to establish analytical data to serve as basis for regulations
the prep of our health products  appropriate authorizations
 to maintain bonded warehouses  post marketing surveillance system
 ban recall and/or withdrawal of product  insuance of certificates

“SEC. 4. To carry out the provisions of this Act, there is hereby created an office to be called the Food and Drug
Administration (FDA) in the Department of Health (DOH). Said Administration shall be under the Office of the
Secretary and shall have the following functions, powers and duties:
“(a) To administer the effective implementation of this Act and of the rules and regulations issued pursuant to the
same;
“(b) To assume primary jurisdiction in the collection of samples of health products;
“(c) To analyze and inspect health products in connection with the implementation of this Act;
“(d) To establish analytical data to serve as basis for the preparation of health products standards, and to
recommend standards of identity, purity, safety, efficacy, quality and fill of container;
“(h) To conduct appropriate tests on all applicable health products prior to the issuance of appropriate
authorizations to ensure safety, efficacy, purity, and quality;
“(i) To require all manufacturers, traders, distributors, importers, exporters, wholesalers, retailers, consumers, and
non-consumer users of health products to report to the FDA any incident that reasonably indicates that said
product has caused or contributed to the death, serious illness or serious injury to a consumer, a patient, or any
person;
“(j) To issue cease and desist orders motu propio or upon verified complaint for health products, whether or not
registered with the FDA: Provided, That for registered health products, the cease and desist order is valid for thirty
(30) days and may be extended for sixty (60) days only after due process has been observed;
“(k) After due process, to order the ban, recall, and/or withdrawal of any health product found to have caused the
death, serious illness or serious injury to a consumer or patient, or is found to be imminently injurious, unsafe,
dangerous, or grossly deceptive, and to require all concerned to implement the risk management plan which is a
requirement for the issuance of the appropriate authorization;
“(l) To strengthen the post market surveillance system in monitoring health products as defined in this Act and
incidents of adverse events involving such products;
“(m) To develop and issue standards and appropriate authorizations that would cover establishments, facilities and
health products;
“(n) To conduct, supervise, monitor and audit research studies on health and safety issues of health products
undertaken by entities duly approved by the FDA;
“(o) To prescribe standards, guidelines, and regulations with respect to information, advertisements and other
marketing instruments and promotion, sponsorship, and other marketing activities about the health products as
covered in this Act;
“(p) To maintain bonded warehouses and/or establish the same, whenever necessary or appropriate, as
determined by the director-general for confiscated goods in strategic areas of the country especially at major ports
of entry; and
“(q) To exercise such other powers and perform such other functions as may be necessary to carry out its duties
and responsibilities under this Act.”

 FDA is responsible for safeguarding public health and safety  that is why they must monitor all products
being available in the public. BEFORE BEING available in market  MUST register first in FDA. In case we have
product that are not safe  (1) report to FDA  investigation; (2) always check/secure registration number

SECTION 6  Section 5 of Republic Act No. 3720, as amended, is hereby further amended and new subsections are
added to read as follows:

“(a) The Centers shall be established per major product category that is regulated, namely:
“(1) Center for Drug Regulation and Research (to include veterinary medicine, vaccines and biologicals);
“(2) Center for Food Regulation and Research;
“(3) Center for Cosmetics Regulation and Research (to include household hazardous/urban substances); and
“(4) Center for Device Regulation, Radiation Health, and Research

“These Centers shall regulate the manufacture, importation, exportation, distribution, sale, offer for sale, transfer,
promotion, advertisement, sponsorship of, and/or, where appropriate, the use and testing of health products. The
Centers shall likewise conduct research on the safety, efficacy, and quality of health products, and to institute
standards for the same.

“(b) Each Center shall be headed by a director. The Centers shall be so organized such that each will have, at least,
the following divisions:
“(1) Licensing and Registration Division, which shall be responsible for evaluating health products and
establishments as covered by this Act for the purpose of issuance of authorizations and conditions to be observed;
“(2) Product Research and Standards Development Division, which shall be responsible for the conduct of research,
development of standards and regulations, compliance monitoring, and the oversight and audit of related
researches that would ensure safety, quality, purity and efficacy of health products, as covered in this Act; and
“(3) Laboratory Support Division, which shall be responsible for the conduct of research and appropriate tests and
calibration, analyses and trials of products including, but not limited to, assays, and the conduct of oversight
and/or audit of centers conducting bioavailability and bioequivalence tests and other tests as covered by this Act.
It shall likewise provide direct line support to the centers which shall be separate and distinct per major product
category that is regulated.

“(c) The Administration and Finance Office headed by the deputy director-general for administration and finance
shall have, at least, the following divisions: the Human Resource Development Division; Property and Logistics
Management Division; Human Resource Management Division; Assets and Financial Management Division; and the
Information and Communication Technology Management Division.
“(d) The Policy and Planning Office which shall be under the Office of the Director-General shall have, at least, a
training, advocacy and communications division and shall monitor the performance of the centers for product
research and evaluation and standards development.
“(e) The Field Regulatory Operations Office headed by the deputy director-general for field regulatory operations
shall include, among others, all the field offices, field or satellite laboratories and the regulatory enforcement
units.
“(f) The Legal Services Support Center shall provide legal services to the entire FDA and shall be directly under the
Office of the Director-General.”

“SECTION 7. Section 6 of Republic Act No. 3720, as amended, is hereby further amended, to read as follows:
“(a) The FDA shall be headed by a director-general, with the rank of undersecretary, who shall be tasked, among
others, to determine the needed personnel and, to appoint personnel, below the assistant director level in
coordination with the Secretary of Health.
“(b) The director-general shall be assisted by two (2) deputy directors-general, one for administration and finance
and another for field regulatory operations.
“(c) The director-general and deputy directors-general shall be appointed by the President of the Republic of the
Philippines.
“(d) The director-general shall, preferably, possess either a university degree in medicine or at least the relevant
master’s degree in pharmaceutical sciences or allied sciences, or equivalent executive course in any regulatory
management. In addition, he/she shall have management experience in his/her field of discipline or profession and
in any development, manufacturing, regulatory work or quality assurance of products as covered in this Act.
“(e) The Deputy Director-General for Field Regulatory Operations of the FDA shall, preferably, possess the relevant
master’s degree in pharmaceutical sciences or allied sciences, or equivalent executive course in any regulatory
management. In addition, he/she shall have management experience in his/her field of discipline or profession and
in any development, manufacturing, regulatory work or quality assurance of products as covered in this Act.
“(f) The Deputy Director-General for Administration and Finance of the FDA shall be a certified public accountant
or shall possess a master’s degree in accounting, management, economics or any business course, and must have
management experience in a position related to his/her field of discipline or profession.
“(g) A person who was previously employed in a regular full-time capacity regardless of its consultative designation
at higher management supervisory levels in regulated establishments, including related foundations, shall be
disqualified from appointment as director-general and deputy director-general within three (3) years from
termination of employment with the said establishment or foundation. All persons who are candidates for
appointment as director-general and deputy director-general must disclose all their incomes for the past three (3)
years from all establishments regulated by this Act. The director-general and the two (2) deputy directors-general
shall, upon assumption into office, declare any conflict of interest with any establishment covered by the FDA,
including their foundations.
“(h) Each center and field office shall be headed by a director who shall be assisted by an assistant director. These
directors shall be appointed by the Secretary of Health.
“(i) The existing directors of the Bureau of Health Devices and Technology (BHDT) and division chiefs of the BFAD
shall be given preference for appointment as directors and assistant directors of their respective centers: Provided,
That if the current officers of the BFAD and the BHDT applying for the above positions lack the required third level
civil service eligibility, they will have to comply with the said requirement within three (3) years from their
appointment, otherwise their appointment shall be revoked immediately.”

SECTION 10  "SEC. 11. The following acts and the causing thereof are hereby prohibited:
"(a) The manufacture, importation, exportation, sale, offering for sale, distribution, transfer, non-consumer use,
promotion, advertising, or sponsorship of any health product that is adulterated, unregistered or misbranded.
"(b) The adulteration or misbranding of any health product
"(d) The giving of a guaranty or undertaking
Section 11, subsections (a), (b), (d), (g), (j),(k) and (l) of Republic Act No. 3720, as amended, are hereby further
amended to read as follows:

SECTION 10  "SEC. 11. The following acts and the causing thereof are hereby prohibited:
"(g) The alteration, mutilation, destruction, obliteration, or removal
"(j) not registered health product.
"(k) The manufacture, importation, exportation, sale, offering for sale, distribution, transfer, or retail without the
license to operate
"(l) any health product beyond its expiration or expiry date, if applicable.
Section 11, subsections (a), (b), (d), (g), (j),(k) and (l) of Republic Act No. 3720, as amended, are hereby further
amended to read as follows:

SECTION 11  Section 12, subsection (a) of Republic Act No, 3720, as amended, is hereby further amended to read
as follows:
“SEC.12. (a) Any person who violates any of the provisions of Section eleven hereof shall, upon conviction, suffer
the penalty of imprisonment ranging from (1) year - (10) years or a fine of (P50, 000.00) - (P500,000.00), or both, at
the discretion of the court.
That if the offender is a manufacturer, importer or distributor of any health product, the penalty of (5 to 10) years
imprisonment and a fine of (P500, 000.00) -(P5,000,000.00).

SECTION 13  Section 29-A of Republic Act No. 3720, as amended, is hereby further amended, and new
subsections are added to read as follows:

"SEC. 29-Amenmment: Administrative Sanctions. –

"(1) Cancellation of any authorization w/c may have been granted by FDA or suspension of validity thereof such
period of time as director general nay deem reasonable diction not exceed 1 yr
"(2) A fine of nlt P50, 000.00 - P500,000.00). An additional fine of (P1, 000.00) shall be imposed for each day of
continuing violation
"(3) Destruction and/or appropriate disposition of the subject health

Special Law on Counterfeit Drugs (RA 8203)

 An act of prohibiting counterfeit drugs, providing penalties for violations and appropriating fund therefor.
Signed into law on September 4 1996 by Pres. Fidel V. Ramos
 It is hereby the policy of the State to protect and promote the right to health of the people and instill health
consciousness among them as provided in Section 15 Article 11 of the Constitution.

Section 4  PROHIBITED ACTS

 The following acts are declared unlawful and therefore prohibited:
o The manufacture, sale, or offering for sale, donation, distribution, trafficking, brokering, exportation, or
importation or possession of counterfeit drugs
o Possession of any such counterfeit drugs (counterfeit drugs- have potency/label claim less than 90% =
hence, will not take effect and more prone to ADRs). However, any person found in possession of
counterfeit drugs in violation of this subsection, shall be excepted from liability under the provisions of
this Act after:
1) presentation of sales invoices, official receipts, or other legally acceptable documents evidencing his
purchase thereof from a drugstore, distributor, manufacture, hospital pharmacy or dispensary, or any
other person or place duly licensed to sell and/or dispense drugs or medicines, and indicating therein the
batch and lot numbers, as well as the expiry dates such drugs; or
2) presentation of certificates and other documents evidencing the importation or exportation of the
counterfeit drugs found in his possession as required by existing laws including those documents required
in the preceding paragraph covering the commercial transactions involving counterfeit drugs.
o Forging, counterfeiting, simulating or falsely representing, or without proper authority
o Photocopying, duplicating, altering, printing, transferring, obliterating or removing the approved label
o Making, selling, or concealing any instrument

Section 5  PARTIES LIABLES

The following Persons shall be liable for violation(s) of this act:
 The owner, proprietor, administrator or manager of the drugstore, hospital pharmacy or dispensary,
laboratory or other outlets or premises where the counterfeit drug is found who induces, causes or allows
the commission of any act herein prohibited;
 The registered pharmacist of the outlet where the counterfeit drug is sold or found, who sells or dispenses
such drug to a third party and who has actual or constructive knowledge that said drug is counterfeit; and
The following Persons shall be liable for violation(s) of this act:
 Should the offense be committed by a juridical person the president, general manager, the managing
partner, chief operating officer or the person who directly induces, causes or knowingly allows the
commission of the offense shall be penalized.
Section 7  ADMINISTRATIVE SANCTIONS
Upon finding that the drugs examined are counterfeit and the determination of the parties liable thereof, the
Bureau shall impose any or all of the following sanctions:
 Permanent closure and revocation of its license
 Fine of NLT ₱100,000 and NMT ₱500,000
 Forfeiture, confiscation, and destruction of products found to be counterfeited and the equipment used
 Forfeiture, confiscation, and destruction of products found to be counterfeited and the equipment used
 Cancellation of the license of the pharmacist
 Permanent disqualification of the person engaged in any business activity

Section 8  PENALTIES
The commission of any of the acts prohibited under section 4 and 6 of this Act shall be punished by:
 imprisonment of not less than six (6) months and one (1) day, but not more than six (6) years for mere
possession of counterfeit drugs as provided for in Sec. 4 (b) hereof;
 imprisonment of six (6) years and one (1) day, but not more than ten (10) years or a fine of not less than One
hundred thousand pesos (P100,000) but not more than Five hundred thousand pesos (P500,000) or both such
imprisonment and fine at the discretion of the court in any other case mentioned in Sec. 4 hereof; or
 imprisonment of not less than six (6) months and one (1) day, but not more than two (2) years and four (4)
months if the counterfeit drug is intended for animals; or
 imprisonment of not less than six (6) years and one (1) day, but not more than ten (10) years for any
manufacturer, seller or distributor who shall conceal, substitute, dispose or destroy any drug as may have
been segregated and sealed by the Bureau, or who shall break, alter or tamper any mark or seal used by the
Bureau to identify those segregated drugs as provided for under Sec. 6 (a) of this Act. Any other person who
breaks, alters or tampers any mark or seal used by the Bureau to identify the segregated drugs shall suffer the
penalty of not less than six (6) months and one (1) day, but not more than six (6) years imprisonment; or
 if, as a result of the use of the drug found to be counterfeit, the illness sought to be cured is aggravated or
physical injury or suffering results therefrom, a punishment of imprisonment from twelve (12) years to fifteen
(15) years and a fine ranging from One hundred thousand pesos (P100,000) to Five hundred thousand pesos
(P500,000) shall be meted out; or
 should a counterfeit drug be the proximate cause of death of a victim, who unknowingly purchased and took a
counterfeit drug, the penalty of life imprisonment and a fine of Five hundred thousand pesos (P500,000) to
Five million pesos (P5,000,000) shall be imposed.

Generics Act of 1988 (RA 6675)

 Approved: Sept 13, 1988 by Corazon Aquino
 AN ACT TO PROMOTE, REQUIREAND ENSURETHE PRODUCTION OF AN ADEQUATE SUPPLY, DISTRIBUTION, USE
AND ACCEPTANCE OF DRUGS AND MEDICINES IDENTIFIED BY THEIR GENERIC NAMES/ Non-proprietary name

Section 2  Statement of Policy

 To promote, encourage and require the use of generic terminology in the importation, manufacture,
distribution, marketing, advertising and promotion, prescription and dispensing of drugs;
 To ensure the adequate supply of drugs with generic names at the lowest possible cost and endeavor to make
them available for free to indigent patients;
 To encourage the extensive use of drugs with generic names through a rational system of procurement and
distribution;
 To emphasize the scientific basis for the use of drugs, in order that health professionals may become more
aware and cognizant of their therapeutic effectiveness; and
 To promote drug safety by minimizing duplication in medications and/or use of drugs with potentially adverse
drug interactions.

Section 4  The Use of Generic Terminology for Essential Drugs and Promotional Incentives
- In the promotion of the generic names for pharmaceutical products, special consideration shall be given to drugs
and medicines which are included in the Essential Drugs List
- The exclusive use of generic terminology in the manufacture, marketing and sales of drugs and medicines,
particularly those in the Essentiall Drugs List.

• Generic drugs should be same or equivalent effect/ quality of branded

• All drugs registered to FDA
• Physician they must prescribe accordingly to generic name

Section 5  POSTING AND PUBLICATION

The Department of Health shall publish annually in at least two (2) newspapers of general circulation in the
Philippines the generic names, and the corresponding brand names under which they are marketed, of all drugs
and medicines available in the Philippines.

Section 6  Who Shall Use Generic Terminology

(a) All government health agencies and their personnel as well as other government agencies shall use generic
terminology or generic names in all transactions related to purchasing, prescribing, dispensing and administering
of drugs and medicines.
(b) All medical, dental and veterinary practitioners, including private practitioners, shall write prescriptions using
the generic name. The brand name may be included if so desired.
(c) Any organization or company involved in the manufacture, importation, repacking, marketing and/or
distribution of drugs and medicines shall indicate prominently the generic name of the product. In the case of
brand name products, the generic name shall appear prominently and immediately above the brand name in all
product labels as well as in advertising and other promotional materials.
(d) Drug outlets, including drugstores, hospital and non-hospital pharmacies and non-traditional outlets such as
supermarkets and stores, shall inform any buyer about any and all other drug products having the same generic
name, together with their corresponding prices so that the buyer may adequately exercise, his option.
Within one (1) year after approval of this Act, the drug outlets referred to herein, shall post in conspicuous places
in their establishments, a list of drug products with the same generic name and their corresponding prices.

Section 7  Provision on Quality, Manufacturer’s Identity and Responsibility –

In order to assure responsibility for drug quality in all instances, the label of all drugs and medicines shall have the
following: name and country of manufacture, dates of manufacture and expiration. The quality of such generically
labeled drugs and medicines shall be duly certified by the Department of Health .
Section 8  Required Production
Subject to the rules and regulations promulgated by the Secretary of Health, every drug manufacturing company
operating in the Philippines shall be required to produce, distribute and make available to the general public the
medicine it produces, in the form of generic drugs.

Section 11  Education Drive – PIA, DOH, DILG, DepEd

The Department of Health jointly with the Department of Education, Culture and Sports, Philippine Information
Agency and the Department of Local Government shall conduct a continuous information campaign for the public
and a continuing education and training for the medical and allied medical professions on drugs with generic
names as an alternative of equal efficacy to the more expensive brand name drugs. Such educational campaign
shall include information on the illnesses or symptoms which each generically named drug is supposed to cure or
alleviate, as well as its contraindications. The Department of Health with the assistance of the Department of Local
Government and the Philippine Information Agency shall monitor the progress of the education drive, and shall
submit regular reports to Congress.

Section 12  Penalty –
A) Any person who shall violate Section 6(a) or 6(b) of this Act shall suffer the penalty graduated hereunder, viz:
(a) for the first conviction, he shall suffer the penalty of reprimand which shall be officially recorded in the
appropriate books of the Professional Regulation Commission.
 (b) for the second conviction, the penalty of fine in the amount of not less than two thousand pesos
(P2,000.00) but not exceeding five thousand pesos (5,000.00) at the discretion of the court.
(c) for the third conviction, the penalty of fine in the amount of not less than five thousand pesos
(P5,000.00) but not exceeding then thousand pesos (P10,000.00) and suspension of his license to practice
his profession for thirty (30) days at the discretion of the court.
(d) for the fourth and subsequent convictions, the penalty of fine of not less than ten thousand pesos
(P10,000.00) and suspension of his license to practice his profession for one year or longer at the
discretion of the court.

B) Any juridical person who violates Section 6(c), 6(d), 7 or 8 shall suffer the penalty of a fine of not less than five
thousand pesos (P5,000.00) nor more than ten thousand pesos (P10,000.00) and suspension or revocation of
license to operate such drug establishment or drug outlet at the discretion of the Court: Provided, that its officers
directly responsible for the violation shall suffer the penalty of fine and suspension or revocation of license to
practice profession, if applicable, and by imprisonment of not less than six (6) months nor more than one (1) year
or both fine and imprisonment at the discretion of the Court: and Provided, further, That if the guilty party is an
alien, he shall be ipso facto deported after service of sentence without need of further proceedings. C) The
Secretary of Health shall have the authority to impose administrative sanctions such as suspension or cancellation
of license to operate or recommend suspension of license to practice profession to the Professional Regulation
Commission as the case may be for the violation of this Act.

Department Memo 2009-0009 (Generics Only Prescribing)

 Issued on January 7, 2009
 This prohibits government physicians to prescribe branded medicines  generics are only allowed

A.O 62 s. 1989 (Subject: Rules and Regulations to Implement Prescribing Requirement s under RA 6675)
Section 3:
- Generic names shall be used in all prescriptions. Section 4: INCORRECT PRESCRIPTIONS
- The generic name must be written in full but the - Erroneous prescription
salt may be abbreviated e.g. Dextromethorphan HCl, - Violative Prescription
Morphine SO4 - Impossible Prescription
- The generic name of the drug must be clearly
written on the prescription immediately after the Rx
symbol

1. ERRONEOUS PRESCRIPTION (error)  DO NOT DIPENSED, and report nearest DOH

 brand name preceded generic name, office, if encounter  call the physical to verify
 generic in parenthesis, and remind physician proper way to write
 brand name not written parenthesis, prescription.
 if encounter √DISPENSED however, collect
prescription and report to DOH office for 3. IMPOSSIBLE PRESCRIPTION
appropriate action  generic written, but not legible
 generic name not corresponds brand name
2. VIOLATIVE PRESCRIPTION (VIOLATION)  generic name and brand name not legible
 "no substitution"  product is not FDA registered (e.g.
 generic name not written Misoprostol/Cytotec)
 generic name is not legible, but brand name  DO NOT DISPENSED,  report to the nearest
legible DOH office and reach out physician.
AO 90 s. 1990 (Subject: Amendment to AO 62 s. 1989 Rules and Regulations to Implement Prescribing
Requirements)
As amended by AO 62, permits the writing of the generic name of more than one drug product in one prescription
form

AO 63 s. 1989 (Subject: Rules and Regulations to Implement Dispensing Requirements under RA 6675)
Section 4  Guidelines on what to do with violative, erroneous, and impossible Rx
1. Violative and impossible Rx  The prescriptions shall be kept and reported by the pharmacist or other
interested parties to the nearest DOH office for appropriate action.
2. Erroneous Rx  The prescriptions shall be filled, but it shall also be kept and reported to the nearest DOH office
for appropriate action.

Section 5  Violations on the part of dispensers and outlets

 Imposing a particular brand or production the buyer
 Inaccurate dispensing
 Failure to post or make accessible required up- to- date info on drug product
 Failure to adequately inform the buyer on available products that meet the prescription
 Failure to indicate the generic name
 Failure to record and keep prescriptions filled.
 Failure to report to the nearest DOH office cases of violative, erroneous, and/or wrong prescriptions within 3
months after receipt of such prescriptions.

Universally Accessible Cheaper and Quality Medicines Act of 2008 (Republic Act 9502)
 Approval Date: June 6, 2008
 An Act Providing for Cheaper and Quality Medicines, Amending for the Purpose Republic Act No. 8293 or The
Intellectual Property Code, Republic Act No. 6675 or The Generics Act of 1988, and Republic Act No. 5921or
The Pharmacy Law and for Other Purposes.

CHAPTER 1: General Provisions

Section 2  Declaration of Policy

It is the policy of the State to protect public health and when the public interest or circumstances of extreme
urgency so require, it shall adopt appropriate measures to promote and ensure access to affordable quality drugs
and medicines for all.
Pursuant to the attainment of this general policy, an effective competition policy in the supply and demand of
quality affordable drugs and medicines is recognized by the State as a primary instrument. In the event that full
competition is not effective, the State recognizes as a reserve instrument the regulation of prices of drugs and
medicines, with clear accountability by the implementing authority as mandated in this Act, as one of the means to
also promote and ensure access to quality affordable medicines (e.g. EXPIRATION OF THE PATENT OF BRANDED 
generic counterpart can now be  approved/patented and x monopolized  to improve and innovate bcs of
competition)

Section 3  Construction in Favor of Protection of Public Health

All doubts in the implementation and interpretation of the provisions of this Act, including its implementing rules
and regulations, shall be resolved in favor of protecting public health.

CHAPTER 3: DRUGS AND MEDICINES PRICE REGULATION

Section 17  Drugs and Medicines Price Regulation Authority of the President of the Philippines.
The President of the Philippines, upon recommendation of the Secretary of the Department of Health, shall have
the power to impose maximum retail prices over any or all drugs and medicines as enumerated in Section 23.

The power to impose maximum retail prices over drugs and medicines shall be exercised within such period of
time as the situation may warrant as determined by the President of the Philippines. No court, except the Supreme
Court of the Philippines, shall issue any temporary restraining order or preliminary injunction or preliminary
mandatory injunction that will prevent the immediate execution of the exercise of this power of the President of
the Philippines.

Section 18  Drugs and Medicines Price Monitoring and Regulation Authority of the Secretary of the
Department of Health.
To implement the policies of this Act under this Chapter, the Secretary of the Department of Health is hereby
authorized to establish and initiate a price monitoring and regulation system for drugs and medicines within one
hundred twenty (120) days after the enactment of this Act. The Secretary of the Department of Health may also
create such bodies, consultative councils, from which advice may be sought in the implementation of a drug or
medicine price monitoring and regulation policy. Such bodies or consultative councils created by the Secretary of
the Department of Health shall coordinate its efforts together with other government agencies .

Section 19  Functions and Responsibilities of the Secretary of the Department of Health. - Pursuant to Section
18 of this Act, the Secretary of the Department of Health shall have the following powers:

 No retailer shall sell drugs and medicines at a retail price exceeding the maximum retail price approved by the
President of the Philippines
 Power to Impose Administrative Fines and Penalties - After due notice and hearing, the Secretary of the
Department of Health shall have the power to impose administrative fines against any person, manufacturer,
importer, trader, distributor, wholesaler, retailer, or any other entity, in such amount as it may deem
reasonable, which in no case shall be less than Fifty thousand pesos (Php50,000.00) nor more than Five million
pesos (Php5,000,000.00) for violations of the maximum retail price approved by the President of the
Philippines pursuant to the provisions of this Chapter.

Section 23  List of Drugs and Medicines that are Subject to Price Regulation - The list of drugs and medicines
that are subject to price regulation shall include, inter alia:

(a) All drugs and medicines indicated for treatment of chronic illnesses and life threatening conditions, such as, but
not limited to, endocrine disorders, e.g., diabetes mellitus; gastrointestinal disorders, e.g., peptic ulcer; urologic
disorders, e.g., benign prostatic hyperplasia (BPH); cardiovascular diseases, e.g., hypertension; pulmonary diseases,
e.g., pulmonary tuberculosis (PTB), asthma; auto-immune diseases, e.g., systemic lupus erythematosus (SLE); skin
diseases, e.g., psoriasis; neuro-psychiatric disorders; other infectious diseases, e.g., human immunodeficiency
virus-acquired immune deficiency syndrome (HIV-AIDS); and other conditions such as organ transplants and
neoplasm;
(b) Drugs and medicines indicated for prevention of diseases, e.g., vaccines, immunoglobulin, anti-sera;
(c) Drugs and medicines indicated for prevention of pregnancy, e.g., oral contraceptives;
(d) Anesthetic agents;
(e) Intravenous fluids;
(f) Drugs and medicines that are included in the Philippine National Drug Formulary (PNDF) Essential Drug List; and
(g) All other drugs and medicines which, from time to time, the Secretary of the Department of Health determines
to be in need of price regulation.

Section 26  Display of Maximum Retail Price Fixed and Approved by Order of the President of the Philippines
for Drugs and Medicines Subject to Price Regulation
(a) Within a reasonable period as may be determined by the Secretary of the Department of Health, and:
Provided, That it conforms to existing drug product labeling requirements, every manufacturer, importer,
distributor, wholesaler, trader, or retailer of a drug and medicine intended for sale shall display the retail price
which shall not exceed the maximum retail price approved by order of the President of the Philippines. The
maximum retail price shall be printed on the label of the immediate container of the drug and medicine and the
minimum pack thereof offered for retail sale with the words "RETAIL PRICE NOT TO EXCEED" preceding it, and
"UNDER DRUG PRICE REGULATION" on a red strip.

(b) Within a period as may be determined by the Secretary of the Department of Health from time to time, every
manufacturer, importer, or trader shall issue a price list to wholesalers, distributors, retailers and to the Secretary
of the Department of Health, indicating the retail price, the maximum retail price, and such other information as
may be required by the Secretary of the Department of Health.

CHAPTER 4: STRENGTHENING OF THE BUREAU OF FOOD AND DRUGS

Section 31  Strengthening of the Bureau of Food and Drugs (BFAD)

The Bureau of Food and Drugs shall submit a yearly performance report to the Quality Affordable Medicines
Oversight Committee, as provided in Section 45 of this Act. The report shall itemize the use of such retained funds
in the past year up to the present and the budgeted use of the same in the succeeding periods.

Section 32  Quality Assurance of Drugs - The Bureau of Food and Drugs shall take the necessary steps to ensure
that all drugs authorized for marketing in the country shall conform to international standards for the content,
purity and quality of pharmaceutical products as established in the International Pharmacopoeia: Provided, That
imported products in finished dosage forms, should be certified under the World Health Organization (WHO)
certification scheme on the quality of pharmaceutical products moving in international commerce: Provided,
further, That the registration for multisource pharmaceutical products should conform to the WHO guidelines on
registration requirements to establish interchangeability .

LABELING REQUIREMENTS
AO 55  Principal display panel-refers to the part of a label that is most likely to be displayed, presented, shown
or examined under customary condition of display for retail use
 If brand name is presented using a special typeface exclusively designed and used for it, the generic name
shall be rendered in Helvetica Medium
 The Rx symbol should be printed in a type size NO LESS THAN one fifth (1/5) of the height of the PDP
 Alcohol content when present must be expressed in %
 Expiration date-shall be expressed in terms of the month and the year.(Last day of the MONTH 03/22 
03/31/22)

DEFINITION OF TERMS
 Warnings - refers to statements regarding the occurrence of potential hazards and side effects associated with
the use of the product and the limitation of its use.
 Contraindications - refers to statements regarding the conditions wherein the use of the product may cause
harm to the patient.
 Precautions - refers to the instruction and special care required in the used of the product to avoid undesired
effects and to ensure the safe and effective use of the drug.

THE PRICE ACT (Republic Act No. 7581)

 May 27, 1992 by Corazon Aquino
 An act providing protection to consumers by stabilizing the prices of basic
necessities and prime commodities and by prescribing measures against undue
price increases during emergency situations and like occasions

Section 2  Declaration of Basic Policy – It is the policy of the State to ensure the availability of basic necessities
and prime commodities at reasonable prices at all times without denying legitimate business a fair return on
investment. It is also a declared policy of the State to provide effective and sufficient protection to consumers
against hoarding, profiteering and cartels with respect to the supply, distribution, marketing and pricing of said
goods, especially during periods of calamity, emergency, widespread illegal price manipulation and other similar
situations. To these ends, the State shall:

(1) Develop, adopt and promulgate measures to promote productivity in basic necessities and prime commodities;
(2) Develop an improved and efficient transport and distribution system;
(3) Develop, adopt and promulgate measures to stabilize prices at reasonable levels;
(4) Institute appropriate penalties for illegal price manipulation and other violations of this Act; and
(5) Establish a mechanism that will readily protect consumers from inadequate supply and unreasonable price
increase on occasions of calamities, emergencies and like occurrences.

Section 5  Illegal Acts of Price Manipulation. – Without prejudice to the provisions of existing laws on goods not
covered by this Act, it shall be unlawful for any person habitually engaged in the production, manufacture,
importation, storage, transport, distribution, sale or other methods of disposition of goods to engage in the
following acts of price manipulation of the price of any basic necessity or prime commodity:

(1) Hoarding, which is the undue accumulation/ buying of bulk/ large amount by a person or combination
of persons of any basic commodity beyond his or their normal inventory levels or the unreasonable
limitation or refusal to dispose of, sell or distribute the stocks of any basic necessity of prime commodity
to the general public or the unjustified taking out of any basic necessity or prime commodity from the
channels of reproduction, trade, commerce and industry.
(2) Profiteering, which is the sale or offering for sale of any basic necessity or prime commodity at a price
grossly in excess of its true worth (hoard/buy at large amount  resell at higher price). Taking advantage
of unusual and exceptional circumstances to make excessive profits
(3) Cartel, which is any combination of or agreement between two (2) or more persons engaged in the
production, manufacture, processing, storage, supply, distribution, marketing, sale or disposition of any
basic necessity or prime commodity designed to artificially and unreasonably increase or manipulate its
price. Groupings of producers that work together to protect their interests and created when a large
groups decides to cooperate with respect to their market  manipulate the price  no competition

Section 6  Automatic Price Control – Unless otherwise declared by the President, prices of basic necessities in an
area shall automatically be frozen at their prevailing prices or placed under automatic price control whenever:

(1) That area is proclaimed or declared a disaster area or under a state of calamity  price freeze;
(2) That area is declared under an emergency;
(3) The privilege of the writ of habeas corpus (arrest  with no warrant) is suspended in that area;
(4) That area is placed under martial law;
(5) That area is declared to be in a state of rebellion; or
(6) A state of war is declared in that area.

Section 7  Mandated Price Ceiling – The President, upon the recommendation of the implementing agency, or
the Price Coordinating Council, may impose a price ceiling on any basic necessity or prime commodity if any of the
following conditions so warrants:

(1) The impendency, existence, or effects of a calamity;

(2) The threat, existence, or effect of an emergency;
(3) The prevalence or widespread acts of illegal price manipulation:
(4) The impendency, existence, or effect of any event that causes artificial and unreasonable increase in the price
of the basic necessity or prime-commodity; and
(5) Whenever the prevailing price of any basic necessity or prime commodity has risen to unreasonable levels.

Section 8  Determination of Price Ceilings – In determining the reasonable price ceiling, the following factors
may be taken into consideration:

(1) The average price, in the last three (3) months immediately preceding the proclamation of the price ceiling, of
the basic necessity or prime commodity under consideration;
(2) The supply available in the market;
(3) The cost to the producer, manufacturer, distributor or seller including but not limited to:

(a) The exchange rate of the peso to the foreign currency with which a basic necessity or prime commodity or any
component, ingredient or raw material thereof was paid for;
(b) Any change in the amortization cost of machinery brought about by any change in the exchange rate of the
peso to the foreign currency with which the machinery was bought through credit facilities;
(c) Any change in the cost of labor brought about by a change in the minimum wage; and
(d) Any increase in the cost of transporting or distributing the basic necessity or prime commodity to the area of
destination.

(4) Such other factors or conditions which will aid in arriving at a just and reasonable price ceiling.

Section 11  Price Coordinating Council – There is hereby created a Price Coordinating Council, hereinafter
referred to as the Council, to be composed of the following members:

(1) The Secretary of Trade and Industry, as Chairman;

(2) The Secretary of Agriculture;
(3) The Secretary of Health;
(4) The Secretary of Environment and Natural Resources;
(5) The Secretary of Local Government;
(6) The Secretary of Transportation and Communications;
(7) The Secretary of Justice;
(8) The Director General of the National Economic and Development Authority;
(9) One (1) representative from the consumers’ sector;
(10) One (1) representative from the agricultural producers’ sector;
(11) One (1) representative from the trading sector; and
(12) One (1) representative from the manufacturers’ sector.

The sectoral representatives of the Price Coordinating Council shall be appointed by the President for a term of
one (1) year, without prejudice to reappointment for another term.

The Council shall meet every quarter and whenever the President or the Chairman shall convene the same. Each
member shall receive reasonable reimbursements for transportation.

Members from the government sector may designate their representative to the Council;

The Department of Trade and Industry shall provide the secretariat to the Council from its existing organizational
structure.

Section 12  Functions of the Price Coordinating Council – The Price Coordinating Council shall have the following
functions

(1) It shall coordinate the productivity, distribution and price stabilization programs, project and measures of the
Government and develop comprehensive strategies to effect a general stabilization of prices of basic necessities
and prime commodities at affordable levels;
(2) It shall report to the President and to the Congress of the Philippines the status and progress of the programs,
projects, and measures undertaken by each implementing department, agency or office as well as the
comprehensive strategies developed by the Council to stabilize the prices of basic necessities and prime
commodities;
(3) It shall advise the President on general policy matters for promotion and improvement in productivity,
distribution and stabilization of prices of basic necessities and prime commodities;
(4) It may require from its members or any other government agency such information as it may deem necessary,
and conduct public hearings for purposes of assessing the supply, distribution and price situation of any basic
necessity or prime commodity;
(5) It shall publicize from time to time developments in productivity, supply, distribution and prices of basic
necessities and prime commodities; and
(6) Whenever automatic price control of basic necessities is imposed under Section 6 of this Act, it shall cause the
immediate dissemination of their prevailing prices or the price ceilings imposed in lieu thereof, as the case may be,
through publication in a newspaper of general circulation in the area affected, and through broadcast by radio and,
whenever the same is deemed to materially make dissemination of the information more effective, by television. It
may also disseminate the information through posting in public markets, supermarkets and other public places.

Section 14  Role of the National Statistics Office – The National Statistics Office shall conduct independent
periodic surveys and studies of the selling prices of all basic necessities and prime commodities all over the country
as well as their share or effect on the family income of the different economic groups in the country for purposes
of serving as data base for government efforts to stabilize prices, as well as evaluating the effectivity of the same.

Section 15  Penalty for Acts of Illegal Price Manipulation – Any person who commits any act of illegal price
manipulation of any basic necessity or prime commodity under Section 5 hereof shall suffer the penalty of
imprisonment for a period of not less than five (5) years nor more than Fifteen (15) years, and shall be imposed a
fine of not less than Five thousand pesos (P5, 000) nor more than Two million pesos (P2, 000, 000).

Section 16  Penalty for Violation of Price Ceiling – Any person who violates Section 6 or 7 of this Act shall suffer
the penalty of imprisonment for a period of not less than one (1) year nor more than ten (10) years of a fine of
note less than Five thousand pesos (P5, 000) nor more than One million pesos (P1, 000, 000), or both, at the
discretion of the court.

Section 18  Violation by Aliens – In case of aliens, in addition to the penalty provided in Section 15 or 16 of this
Act, the offender shall, upon conviction and after service of sentence, be immediately deported without need of
any further proceedings.

Section 19  Violation by Government Officials or Employees – Any public official or employee who, by reason of
his office, with or without consideration, conspires in the commission or knowingly conceals violations of any of
the provisions of this Act shall likewise be principally responsible for the violation and shall suffer the additional
penalty of permanent disqualification to hold public office.

Expanded Senior Citizens Act of 2010 (RA 9994)

 An act granting additional benefits and privileges to senior citizens, further amending republic act no. 7432, as
amended, otherwise known as “an act to maximize the contribution of senior citizens to nation building, grant
benefits and special privileges and for other purposes”
 Signed into law on February 14, 2010 by President Macapagal Arroyo
 RA 7432 (Senior Citizen Act of 1992) Date Signed: April 23, 1992  RA 9257 (Expanded Senior Citizens Act of
2003 Date Signed: February 26, 2004)  RA 9994 (Expanded Senior Citizens Act of 2010) Date Signed:
February 15 2010

Section 2  Declaration of Policies and Objectives

“(a) To recognize the rights of senior citizens to take their proper place in society and make it a concern of the
family, community, and government;
“(b) To give full support to the improvement of the total well-being of the elderly and their full participation in
society, considering that senior citizens are integral part of Philippine society;
“(c) To motivate and encourage the senior citizens to contribute to nation building;
“(d) To encourage their families and the communities they live with to reaffirm the valued Filipino tradition of
caring for the senior citizens;
“(e) To provide a comprehensive health care and rehabilitation system for disabled senior citizens to foster their
capacity to attain a more meaningful and productive ageing; and
“(f) To recognize the important role of the private sector in the improvement of the welfare of senior citizens and
to actively seek their partnership
“In accordance with these objectives, this Act shall:
“(1) establish mechanisms whereby the contributions of the senior citizens are maximized;
“(2) adopt measures whereby our senior citizens are assisted and appreciated by the community as a whole;
“(3) establish a program beneficial to the senior citizens, their families and the rest of the community they serve:
and
“(4) establish community-based health and rehabilitation programs for senior citizens in every political unit of
society”

Section 4  Privileges for the Senior Citizens –

The senior citizens shall be entitled to the following:
“(a) the grant of twenty percent (20%) discount and exemption from the value -added tax (VAT), if applicable, on
the sale of the following goods and services from all establishments, for the exclusive use and enjoyment or
availment of the senior citizen
 “(1) on the purchase of medicines, including the purchase of influenza and pnuemococcal vaccines, and such
other essential medical supplies, accessories and equipment to be determined by the Department of Health
(DOH).
 “The DOH shall establish guidelines and mechanism of compulsory rebates in the sharing of burden of
discounts among retailers, manufacturers and distributors, taking into consideration their respective
margins;
 “(2) on the professional fees of attending physician/s in all private hospitals, medical facilities, outpatient
clinics and home health care services;
 “(3) on the professional fees of licensed professional health providing home health care services as
endorsed by private hospitals or employed through home health care employment agencies;
 “(4) on medical and dental services, diagnostic and laboratory fees in all private hospitals, medical facilities,
outpatient clinics, and home health care services, in accordance with the rules and regulations to be issued
by the DOH, in coordination with the Philippine Health Insurance Corporation (PhilHealth);
 “(5) in actual fare for land transportation travel in public utility buses (PUBs), public utility jeepneys (PUJs),
taxis, Asian utility vehicles (AUVs), shuttle services and public railways, including Light Rail Transit (LRT),
Mass Rail Transit (MRT), and Philippine National Railways (PNR);
 “(6) in actual transportation fare for domestic air transport services and sea shipping vessels and the like,
based on the actual fare and advanced booking;
 “(7) on the utilization of services in hotels and similar lodging establishments, restaurants and recreation
centers;
 “(8) on admission fees charged by theaters, cinema houses and concert halls, circuses, leisure and
amusement; and
 “(9) on funeral and burial services for the death of senior citizens;
“(b) exemption from the payment of individual income taxes of senior citizens who are considered to be minimum
wage earners in accordance with Republic Act No. 9504;
“(c) the grant of a minimum of five (5%) discount relative to the monthly utilization of water and electricity
supplied by the public utilities: Provided, That the individual meters for the foregoing utilities are registered in the
name of the senior citizen residing therein: Provided, further, That the monthly consumption does not exceed one
hundred kilowatt hours (100 kWh) of electricity and thirty cubic meters (30 m3) of water: Provided,
furthermore, That the privilege is granted per household regardless of the number of senior citizens residing
therein;
“(d) exemption from training fees for socioeconomic programs;
“(e) free medical and dental services, diagnostic and laboratory fees such as, but not limited to, x-rays,
computerized tomography scans and blood tests, in all government facilities, subject to the guidelines to be issued
by the DOH in coordination with the PhilHealth;
“(f) the DOH shall administer free vaccination against the influenza virus and pneumococcal disease for indigent
senior citizen patients;
“(g) educational assistance to senior citizens to pursue pot secondary, tertiary, post tertiary, vocational and
technical education, as well as short-term courses for retooling in both public and private schools through
provision of scholarships, grants, financial aids, subsides and other incentives to qualified senior citizens, including
support for books, learning materials, and uniform allowances, to the extent feasible: Provided, That senior
citizens shall meet minimum admission requirements;
“(h) to the extent practicable and feasible, the continuance of the same benefits and privileges given by the
Government Service Insurance System (GSIS), the Social Security System (SSS) and the PAG-IBIG, as the case may
be, as are enjoyed by those in actual service;
“(i) retirement benefits of retirees from both the government and the private sector shall be regularly reviewed to
ensure their continuing responsiveness and sustainability, and to the extent practicable and feasible, shall be
upgraded to be at par with the current scale enjoyed by those in actual service;
“(j) to the extent possible, the government may grant special discounts in special programs for senior citizens on
purchase of basic commodities, subject to the guidelines to be issued for the purpose by the Department of Trade
and Industry (DTI) and the Department of Agriculture (DA);
“(k) provision of express lanes for senior citizens in all commercial and government establishments; in the absence
thereof, priority shall be given to them; and
“(l) death benefit assistance of a minimum of Two thousand pesos (Php2, 000.00) shall be given to the nearest
surviving relative of a deceased senior citizen which amount shall be subject to adjustments due to inflation in
accordance with the guidelines to be issued by the DSWD.

“In the availment of the privileges mentioned above, the senior citizen, or his/her duly authorized representative,
may submit as proof of his/her entitled thereto any of the following:
 “(1) an identification card issued by the Office of the Senior Citizen Affairs (OSCA) of the place where the
senior citizen resides: Provided, That the identification card issued by the particular OSCA shall be
honored nationwide;
 “(2) the passport of the senior citizen concerned; and
 “(3) other documents that establish that the senior citizen is a citizen of the Republic and is at least sixty
(60) years of age as further provided in the implementing rules and regulations

Section 6  The Office for Senior Citizens Affairs (OSCA) – There shall be established in all cities and
municipalities an OSCA to be headed by a senior citizen who shall be appointed by the mayor for a term of three
(3) years without reappointment but without prejudice to an extension if exigency so requires. Said appointee
shall be chosen from a list of three (3) nominees as recommended by a general assembly of senior citizens
organizations in the city or municipality.
“The head of the OSCA shall be appointed to serve the interest of senior citizens and shall not be removed or
replaced except for reasons of death permanent disability or ineffective performance of his duties to the detriment
of fellow senior citizens.
“The head of the OSCA shall be entitled to receive an honorarium of an amount at least equivalent to Salary
Grade 10 (P 20, 219) to be approved by the LGU concerned.
“The head of the OSCA shall be assisted by the City Social Welfare and Development officer or by the Municipal
Social Welfare and Development Officer, in coordination with the Social Welfare and Development Office.
“The Office of the Mayor shall exercise supervision over the OSCA relative to their plans, activities and programs
for senior citizens. The OSCA shall work together and establish linkages with accredited NGOs Pos and the
barangays in their respective areas.
“The OSCA shall have the following functions:
“(a) To plan, implement and monitor yearly work programs in pursuance of the objectives of this Act;
“(b) To draw up a list of available and required services which can be provided by the senior citizens;
“(c) To maintain and regularly update on a quarterly basis the list of senior citizens and to issue national individual
identification cards, free of charge, which shall be valid anywhere in the country;
“(d) To serve as a general information and liason center for senior citizens;
“(e) To monitor compliance of the provisions of this Act particularly the grant of special discounts and privileges to
senior citizens;
“(f) To report to the mayor, any individual, establishments, business entity, institutions or agency found violating
any provision of this Act; and
“(g) To assist the senior citizens in filing complaints or charges against any individual, establishments, business
entity, institution, or agency refusing to comply with the privileges under this Act before the Department of Justice
(DOJ), the Provincial Prosecutor’s Office, the regional or the municipal trial court, the municipal trial court in cities,
or the municipal circuit trial court.”

“Section 10  Penalties – Any person who refuses to honor the senior citizen card issued by this the government
or violates any provision of this Act shall suffer the following penalties:
“(a) For the first violation, imprisonment of not less than two (2) years but not more than six (6) years and a fine of
not less than Fifty thousand pesos (Php50,000.00) but not exceeding One hundred thousand pesos
(Php100,000.00);
“(b) For any subsequent violation, imprisonment of not less than two (2) years but not more than six (6) years and
a fine of not less than One Hundred thousand pesos (Php100,000.00) but not exceeding Two hundred thousand
pesos (Php200,000.00); and
“(c) Any person who abuses the privileges granted herein shall be punished with imprisonment of not less than six
(6) months and a fine of not less than Fifty thousand pesos (Php50,000.00) but not more than One hundred
thousand pesos (Php100,000.00).
“If the offender is a corporation, partnership, organization or any similar entity, the officials thereof directly
involved such as the president, general manager, managing partner, or such other officer charged with the
management of the business affairs shall be liable therefor.
“If the offender is an alien or a foreigner, he/she shall be deported immediately after service of sentence.
“Upon filing of an appropriate complaint, and after due notice and hearing, the proper authorities may also cause
the cancellation or revocation of the business permit, permit to operate, franchise and other similar privileges
granted to any person, establishment or business entity that fails to abide by the provisions of this Act.”

Comprehensive Dangerous Drugs Act of 2002 (RA 9165)

 AN ACT INSTITUTING THE COMPREHENSIVE DANGEROUS DRUGS ACT OF 2002, repealing R.A. 6425, otherwise
known as the THE DANGEROUS DRUGS ACT OF 1972, as amended, providing funds therefor, and for other
purposes.
 Signed into law on June 7, 2002 by Pres. Gloria Macapagal-Arroyo

Section 2  Declaration of Policy

– It is the policy of the State to safeguard the integrity of its territory and the well-being of its citizenry
particularly the youth, from the harmful effects of dangerous drugs on their physical and mental well-being, and
to defend the same against acts or omissions detrimental to their development and preservation. In view of the
foregoing, the State needs to enhance further the efficacy of the law against dangerous drugs, it being one of
today's more serious social ills.
Toward this end, the government shall pursue an intensive and unrelenting campaign against the trafficking and
use of dangerous drugs and other similar substances through an integrated system of planning, implementation
and enforcement of anti-drug abuse policies, programs, and projects. The government shall however aim to
achieve a balance in the national drug control program so that people with legitimate medical needs are not
prevented from being treated with adequate amounts of appropriate medications, which include the use of
dangerous drugs.
It is further declared the policy of the State to provide effective mechanisms or measures to re-integrate into
society individuals who have fallen victims to drug abuse or dangerous drug dependence through sustainable
programs of treatment and rehabilitation.

ARTICLE 9  Dangerous Drugs Board and Philippine Drug Enforcement Agency

Dangerous Drug Board  Implementing Agency of this Act that would be in charge of planning and creating
programs for the pursuance of this Act
 Section 77  DDB: The Board shall be the policy-making and strategy-formulating body in the planning and
formulation of policies and programs on drug prevention and control. It shall develop and adopt a
comprehensive, integrated, unified and balanced national drug abuse prevention and control strategy. It shall
be under the Office of the President.
 Section 78  Composition of the Board – The Board shall be composed of seventeen (17) members wherein
three (3) of which are permanent members, the other twelve (12) members shall be in an ex officio capacity
and the two (2) shall be regular members.
o CURRENTLY: Dangerous Drug Board Chairman: Mr. Catalino Salandanan Cuy; PDEA Director General: Mr.
Wilkins M. Villanueva
o The three (3) permanent members, who shall possess at least seven-year training and experience in the
field of dangerous drugs and in any of the following fields: in law, medicine, criminology, psychology or
social work, shall be appointed by the President of the Philippines. The President shall designate a
Chairman, who shall have the rank of a secretary from among the three (3) permanent members who
shall serve for six (6) years. Of the two (2) other members, who shall both have the rank of
undersecretary, one (1) shall serve for four (4) years and the other for two (2) years. Thereafter, the
persons appointed to succeed such members shall hold office for a term of six (6) years and until their
successors shall have been duly appointed and qualified.
o The other twelve (12) members who shall be ex officio members of the Board are the following:
 (1) Secretary of the Department of Justice or his/her representative;
 (2) Secretary of the Department of Health or his/her representative;
 (3) Secretary of the Department of National Defense or his/her representative;
 (4) Secretary of the Department of Finance or his/her representative;
 (5) Secretary of the Department of Labor and Employment or his/her representative;
 (6) Secretary of the Department of the Interior and Local Government or his/her representative;
 (7) Secretary of the Department of Social Welfare and Development or his/her representative;
 (8) Secretary of the Department of Foreign Affairs or his/her representative;
 (9) Secretary of the Department of Education or his/her representative;
 (10) Chairman of the Commission on Higher Education or his/her representative;
 (11) Chairman of the National Youth Commission;
 (12) Director General of the Philippine Drug Enforcement Agency
o Cabinet secretaries who are members of the Board may designate their duly authorized and permanent
representatives whose ranks shall in no case be lower than undersecretary.
o The two (2) regular members shall be as follows:
(a) The president of the Integrated Bar of the Philippines; and
(b) The chairman or president of a non-government organization involved in dangerous drug campaign to
be appointed by the President of the Philippines.

Section 82  Creation of the Philippine Drug Enforcement Agency (PDEA) – To carry out the provisions of this
Act, the PDEA, which serves as
 the implementing arm of the Board, and
 shall be responsible for the efficient and effective law enforcement of all the provisions on any
dangerous drug and/or controlled precursor and essential chemical as provided in this Act
 The PDEA shall be headed by a Director General with the rank of Undersecretary, who shall be
responsible for the general administration and management of the Agency.
 The Director General of the PDEA shall be appointed by the President of the Philippines and shall perform
such other duties that may be assigned to him/her. He/she must possess adequate knowledge, training
and experience in the field of dangerous drugs, and in any of the following fields: law enforcement, law,
medicine, criminology, psychology or social work.

ARTICLE II: Unlawful Acts and Penalties

IMPRISONMENT FINE
Life imprisonment to death 500K-10M
*reclusion perpetua
2P 12 years 1 day – 20 years 100K-500K
3P 6 months 1 day – 4 years 10K-50K
Maximum penalty  reflects parliament’s view on the seriousness of the offence. Maximum penalties for many
offences, including all offences in the Crimes Act 1958, are set according to a penalty scales, as outlined in the
Sentencing Act 1991)
LEVEL 9 = 6 months
LEVEL 1 = life imprisonment

1P  Life imprisonment to Death (reclusion Perpetua) Fine: Php 500,000 to 10 Million

 Importation of Dangerous Drugs  Sale of Dangerous Drugs
 Manufacture of Dangerous Drugs  Cultivation or Culture
 Unlawful Prescription  Maintenance of Den, Dive or Resort of
 Possession of Dangerous Drugs Dangerous Drugs

Section 11  Possession of Dangerous Drugs - The penalty of life imprisonment to death and a fine ranging from
Five hundred thousand pesos (P500,000.00) to Ten million pesos (P10,000,000.00) shall be imposed upon any
person, who, unless authorized by law, shall possess any dangerous drug in the following quantities, regardless of
the degree of purity thereof:
 10 grams or more of opium;  10 grams or more of other dangerous drugs
 10 grams or more of morphine; such as, but not limited to,
 10 grams or more of heroin; methylenedioxymethamphetamine (MDA) or
 10 grams or more of cocaine or cocaine "ecstasy", paramethoxyamphetamine (PMA),
hydrochloride; trimethoxyamphetamine (TMA), lysergic acid
 50 grams or more of methamphetamine diethylamine (LSD), gamma
hydrochloride or "shabu"; hydroxyamphetamine (GHB), and those
 10 grams or more of marijuana resin or similarly designed or newly introduced drugs
marijuana resin oil; and their derivatives, without having any
 500 grams or more of marijuana; and therapeutic value or if the quantity possessed
is far beyond therapeutic requirements

2P  Imprisonment of 12 Years 1 day to 20 Years Fine: Php 100,000 to Php 500,000

 Importation of Controlled precursor or Essential chemicals
 Manufacture of Controlled precursor or Essential chemicals
 Unnecessary Prescription
 Illegal diversions of any Controlled precursor or Essential chemicals
 Sale of Controlled precursor or Essential chemicals
 Coddler / Protector
 Maintenance of Den, Dive or Resort of Controlled precursor or Essential chemicals

3P  Imprisonment of 6 Months 1 day to 4 Years Fine: Php 10,000 to Php 50,000

 Possession of Equipment, Instrument, Apparatus and Other Paraphernalia for Dangerous Drugs
 Drug Users

MAXIMUM PENALTY
 Possession of Dangerous Drugs during Parties, Social Gatherings or Meetings.
 Bringing any Dangerous Drugs, Controlled Precursors or Essential Chemicals through the use of Diplomatic
Passport.
 Selling, Trading, Distributing Illegal substances 100 meters away from school.
 Financer and Drug Sellers who use mentally deranged people and minors.

 Death penalty (now: life imprisonment) and 1M - 15M pesos: maintainer, owner and/or operator  Should
any dangerous drug be the proximate cause of the death of a person using the same in such den, dive or
resorts
 (1) year and one (1) day to six (6) years and a fine ranging 10K - 50K  10K - 50K violates or fails to comply
with the maintenance and keeping of the original records of transactions on any dangerous drug and/or
controlled precursor and essential chemical

ARTICLE III: Dangerous Drugs Test and Record Requirements

Section 36  Authorized Drug Testing  Authorized drug testing shall be done by any government forensic
laboratories or by any of the drug testing laboratories accredited and monitored by the DOH to safeguard the
quality of test results. The DOH shall take steps in setting the price of the drug test with DOH accredited drug
testing centers to further reduce the cost of such drug test. The drug testing shall employ, among others, two (2)
testing methods, the screening test which will determine the positive result as well as the type of the drug used
and the confirmatory test which will confirm a positive screening test. Drug test certificates issued by accredited
drug testing centers shall be valid for a one-year period from the date of issue which may be used for other
purposes. The following shall be subjected to undergo drug testing:

MANDATORY TESTING:
(a) Applicants for driver's license. – No driver's license shall be issued or renewed to any person unless he/she
presents a certification that he/she has undergone a mandatory drug test and indicating thereon that he/she is
free from the use of dangerous drugs;
(b) Applicants for firearm's license and for permit to carry firearms outside of residence. – All applicants for
firearm's license and permit to carry firearms outside of residence shall undergo a mandatory drug test to ensure
that they are free from the use of dangerous drugs: Provided, That all persons who by the nature of their
profession carry firearms shall undergo drug testing;
(c) Officers and members of the military, police and other law enforcement agencies. – Officers and members of
the military, police and other law enforcement agencies shall undergo an annual mandatory drug test;
(d) All persons charged before the prosecutor's office with a criminal offense having an imposable penalty of
imprisonment of not less than six (6) years and one (1) day shall have to undergo a mandatory drug test; and
(e) All candidates for public office whether appointed or elected both in the national or local government shall
undergo a mandatory drug test.

RANDOM TESTING:
(a) Students of secondary and tertiary schools. – Students of secondary and tertiary schools shall, pursuant to the
related rules and regulations as contained in the school's student handbook and with notice to the parents,
undergo a random drug testing: Provided, That all drug testing expenses whether in public or private schools under
this Section will be borne by the government;
(b) Officers and employees of public and private offices. – Officers and employees of public and private offices,
whether domestic or overseas, shall be subjected to undergo a random drug test as contained in the company's
work rules and regulations, which shall be borne by the employer, for purposes of reducing the risk in the
workplace. Any officer or employee found positive for use of dangerous drugs shall be dealt with administratively
which shall be a ground for suspension or termination, subject to the provisions of Article 282 of the Labor Code
and pertinent provisions of the Civil Service Law;

Section 40  Records Required for Transactions on Dangerous Drug and Precursors and Essential Chemicals
a) Every pharmacist dealing in dangerous drugs and/or controlled precursors and essential chemicals shall
maintain and keep an original record of sales, purchases, acquisitions and deliveries of dangerous drugs, indicating
therein the following information:
(1) License number and address of the pharmacist;
(2) Name, address and license of the manufacturer, importer or wholesaler from whom the dangerous
drugs have been purchased;
(3) Quantity and name of the dangerous drugs purchased or acquired;
(4) Date of acquisition or purchase;
(5) Name, address and community tax certificate number of the buyer;
(6) Serial number of the prescription and the name of the physician, dentist, veterinarian or practitioner
issuing the same;
 (7) Quantity and name of the dangerous drugs sold or delivered; and
(8) Date of sale or delivery.

A certified true copy of such record covering a period of six (6) months, duly signed by the pharmacist or the owner
of the drugstore, pharmacy or chemical establishment, shall be forwarded to the Board within fifteen (15) days
following the last day of June and December of each year, with a copy thereof furnished the city or municipal
health officer concerned.

(b) A physician, dentist, veterinarian or practitioner authorized to prescribe any dangerous drug shall issue the
prescription therefor in one (1) original and two (2) duplicate copies. The original, after the prescription has been
filled, shall be retained by the pharmacist for a period of one (1) year from the date of sale or delivery of such drug.
One (1) copy shall be retained by the buyer or by the person to whom the drug is delivered until such drug is
consumed, while the second copy shall be retained by the person issuing the prescription.

WHAT ARE THE CHEMICALS CONTROLLED UNDER RA 9165?

The controlled chemicals are the following:
TABLE I+ Table II+
ACETIC ANHYDRIDE ACETONE
N-ACETYLANTHRANILIC ACID ANTHRANILIC ACID
ERGOMETRINE ETHYL ETHER
ERGOTAMINE HYDROCHLORIC ACID
ISOSAFROLE METHYL ETHYL KETONE
LYSERGIC ACID PHENYL ACETIC ACID
3,4-METHYLENEDIOXYPHENYL-2 PROPANONE PIPERIDINE
NOREPHEDRINE SULFURIC ACID
1-PHENYL-2-PROPANONE TOLUENE
PIPERONAL ** THIONYL CHLORIDE
POTASSIUM PERMANGANATE
SAFROLE
* PSEUDOEPHERDINE
* EPHEDRINE
* RECLASSIFIED AS DANGEROUS DRUGS PURSUANT TO B.R. NO. 4, S. 2005
** CLASSIFIED UNDER TABLE II PURSUANT TO B.R. NO. 5,S. 2005
+ THE SALTS OF THE SUBSTANCES LISTED IN THIS TABLE WHENEVER THE EXISTENCE OF SUCH SALTS IS POSSIBLE.
++ THE SALTS OF THE SUBSTANCES LISTED IN THIS TABLE WHENEVER THE EXISTENCE OF SUCH SALTS IS
POSSIBLE.THE SALTS OF HYDROCHLORIC ACID AND SULFURIC ACID ARE SPECIFICALLY EXCLUDED.

WHAT ARE THE LICENSES ISSUED AT THE COMPLIANCE SERVICE, PDEA, AND THE SCOPE OF COVERAGE OF EACH
LICENSE WITH THE CORRESPONDING FEES?

1. For handlers of dangerous drug/s(DD), dangerous drugs preparation/s(DDP/s), Table I Controlled

Chemical/s used in the manufacture of drug preparation/s &/or their preparation/s (DP/s):
Category Annual Fee (PhP)
S-1 Dealer Retail of DP/s containing Table I Controlled Chemical/s 500.00
S-3 Retailer Retail of DD/DDP/s & /or DP/s containing Table I Controlled Chemical/s 1,000.00
S-4 Wholesale/Distribution of DD/DDP/s/Table 1 Controlled Chemical/s used in 3,000.00
Wholesaler the manufacture of drug preparation/s/ &/or their preparation/s
S-5 Compounding/Manufacture of DD/ DDPs &/or D P/s containing Table I 5,000.00
Compounder Controlled Chemical/s
S-5I Importer Importation of DD/DDP/s /Table I Controlled Chemical/s used in the 5,000.00
manufacture of drug preparation/s &/or their preparation/s
S-5E Exporter Exportation of DDP/s &/or D P/s containing Table I Controlled Chemical/s 5,000.00
S-5D Depot/Storage for S-4 & S-5 license holder (When such address is separate 5,000.00
Depot/Storage and distinct from the office address of the license holder)
S-6 License to conduct laboratory analysis or technical research using DD/DDPs 500.00
Researcher &/or DP/s
S-8  Importer and Compounder

2. For handlers of Precursors and Essential Chemical/s or Controlled Chemical/s &/ or mixture/s (PECS)

Category Annual Fee (PhP)

P-1 Retail of Precursor & Essential Chemicals ( PECS) &/or mixture/s 500.00
P-3 End-Use of PECS &/or mixture/s 2,500.00
P-4 Wholesale/Distribution/Trading of PECS&/or mixture/s 3,000.00
P-5-C Compounding/Manufacture/Repack/Recycling of PECS &/or mixture/s 5,000.00
P-5-D Bulk Depot/Storage for P4 & P5-Holders ( Such location is deemed separate& 3,000.00
distinct from the office address of the license holder)
P-5-E Exportation of PECS &/or mixture/s 5,000.00
P-5-I Importation of PECS &/or mixture/s 5,000.00
P-5-IM Importation of PECS to End-Use 5,000.00
P-6 License to conduct laboratory analysis or technical research using PECS 5 500.00

3. For Practitioners (Physician, Dentist, Veterinarian)

Category
S-2 License to prescribe DD/DDPs, &/or DP/s containing Table I Controlled Chemical/s

WHAT ARE THE THRESHOLDS FOR TABLE II CONTROLLED CHEMICAL/S THAT CAN BE SOLD TO A REGULAR OR
KNOWN CUSTOMER IN A MONTHLY BASIS THAT WILL NOT REQUIRE PRESENTING A PDEA LICENSE?
SINGLE COMPONENT CHEMICAL TOTAL
Acetone 1 liter
Hydrochloric acid 25 liters
Sulfuric acid 25 liters
Ethyl ether 1 liter
Toluene 1 liter
METHYL ETHYL KETONE 1 liter
CHEMICAL MIXTURE/SOLUTION AGGREGATE
Cont’g Acetone 5 liters
Cont’g Hydrochloric acid 50 liters
Cont’g Sulfuric acid 50 liters
Cont’g Ethyl ether 5 liters
Cont’g 30% toluene 20 liters
Cont’g 30% toluene Methyl ethyl ketone 5 liters

WHAT ARE THE REQUIREMENTS RELATIVE TO THE SALE OF TABLE II CONTROLLED CHEMICAL THAT FALLS WITHIN
THE PRESCRIBED THRESHOLD ABOVE?
The following are the requirements involving the sale of Table II Controlled Chemical that falls within the
prescribed threshold above:
1. The licensed seller shall ask the customer for any identifying document such as driver’s license, office or voter’s
identification and signature of the individual;
2. Purchased controlled chemical shall not be resold by the purchaser;
3. Table II Controlled chemical shall not be sold to minors who are less than eighteen (18) years of age without the
written consent of his/her parents or guardian or sold for the purpose of abuse;
4. Transaction will be recorded by the licensed seller in a record book /register, which is subject to inspection at
any reasonable time by PDEA Regulatory Compliance Officer;
5. Transaction will be for legitimate use by the purchaser and not for resale.

WHAT ARE THE PRESCRIPTION LIMITS FOR DANGEROUS DRUGS’ PREPARATIONS?

The following are the prescription limits of dangerous drugs’ preparations that may be prescribed in a single
applicable prescription by a licensed practitioner:
A. FOR CANCER PATIENTS:
1. Morphine Sulfate (tablets) 3,000 mg
Morphine Sulfate (ampoules/vials) 448 mg
2. Fentanyl patch 25 ug/hour 30 patches
Fentanyl patch 50 ug/hour 15 patches
Fentanyl ampoules 50 ug/mL  10 ampoules (1mL)
 3 ampoules (2mL)
 50 ampoules (2mL)for use in Patient
 Controlled Analgesic
 (PCA) machine
 10 ampoules (10mL)for use in Patient Controlled
Analgesic (PCA) machine
3. Oxycontin 1,200 mg
Oxycontin 10 mg 120 tablets
Oxycontin 20 mg 60 tablets
Oxycontin 40 mg 30 tablets
Oxycontin 80 mg 15 tablets
4. Demerol 14 vials
5. Dangerous Drugs (ampoules or 20 pieces
hypodermic tablets 40 pieces
Dangerous Drugs (tablets) 40 pieces
B. FOR ORDINARY CIRCUMSTANCES
1. Benzodiazepines (anxiolytic or hypnotic or both) 30 tabs or caps
Benzodiazepines (anxiolytic or hypnotic or both)  30 tabs or caps
 10 ampoules x 1 mL
 3 ampoules x 2 mL
 2 ampoules x 3 mL
 2 ampoules x 5 mL
 1 ampoule x 10 mL
Benzodiazepine (muscle spasm/dystonia/tetanus) 90 tablets (5 mg)
2. Phenobarbital preparations  2 weeks supply
 2 bottles (100 tablet each) for Epileptic patients
3. Sodium Pentothal 3 vials (in case of hospital use)
4. Demerol 3 Ampoules
5. Other Dangerous Drugs (in vials) 1 vial (in case of hospital use)
6. Ephedrine (parenteral form) 1 vial
Ephedrine, pseudoephedrine, norepher drine 1.6 grams of base
(tablet/capsule)

WHAT ARE THE INFORMATION CONTAINED IN A DANGEROUS DRUG PREPARATION’S PRESCRIPTION?

The following are the information contained in a dangerous drug preparation’s prescription:
Date of prescription;
1. Complete name & address of patient;
2. Complete name , address, & telephone number of prescribing practitioner;
3. Prescribing practitioner’s current s-2 license no., prc registration no., & ptr no., & signature;
4. Brand name & generic name, total no. Of units to be supplied in words followed by its roman numeral enclosed
in parenthesis;
5. Direction for use & the words ‘non-repetition.”

IMPORTANT DATES:
RA 6425  The Dangerous Drugs Act of 1972  Date Signed: April 4, 1972
RA 9165  Comprehensive Dangerous Drugs Act of 2002  Date signed: June 7, 2002
Pharmaceutical Dosage Forms and Drug Delivery Systems  Dr. Lyman Spalding
 He was called “ the father of USP”
Drug – an agent used in the diagnosis, mitigation, treatment, cure, or
prevention of diseases in humans and animals.  On December 15, 1820, the first USP was published in English and
Latin, It was a 272-page and 217 drugs were listed in it
Diagnosis - BaSo4
Mitigation – Analgesic (Paracetamol, NSAIDs)  At first, the revision of USP was every 10 years but was decided to
Treatment/Cure – Antibiotics revise it every 5 years (1940)
Prevention – Vaccines, OCPs
 1888, the first National Formulary was published under the title
Development of The Pharmacy Practice “National Formulary of Unofficial Drugs”

 Hippocrates:  1975, US pharmacopoeial convention purchased NF.

 Greek physician who is credited with the introduction of
scientific pharmacy and medicine. (rationally)  1980, the first combined compendium (USP-NF) was published.
 Known as the Father of Medicine
 Theory of humoral pathology  In 1864, the first British Pharmacopoeia

 Pedanius Dioscorides Monograph

 Greek physician and botanist who was the first to deal with
botany as an applied science of pharmacy.  Official Title (Generic Name)
 His work, De Materia Medica, is a milestone in the  Graphic or Structural Formula
development of pharmaceutical botany and in the study of  Empirical Formula
naturally occurring medicinal materials (Pharmacognosy)  Molecular Weight
 Father of Pharmacology  Established Chemical Names
 Botanist/pharmacologist  Chemical Abstracts Service (CAS) Registry Number
 Chemical Purity – in terms of percentage
 Claudius Galen  Cautionary Statement
 First Pharmacist/Botanist associated with galenicals (tinctures,  Packaging
 Storage
fluidextracts, syrups, ointments)
 Chemical and Physical Tests
 Originator of the formula for a cold cream, essentially similar to
 Method of Assay
that known today.
Other References to Drug Standards
 Philippus Aureolus Theophrastus Bombastus von Hohenheim
 Also known as Paracelsus
 Homeopathic Pharmacopoeia of the United States (HPUS)
 Father of Toxicology - Homeopathy: homoios (similar), pathos: (disease)
 A swiss physician and chemist who introduced chemical - Like cures like
science from the traditional botanical science.  International Pharmacopoeia/Pharmacopoeia Internationalis
 Sulfur – combustibility (Published by WHO)
 Mercury – liquidity  British Pharmacopoeia
 Salt – stability  European Pharmacopoeia

 Karl Wilhelm Scheele New Drug Development and Approval Process

 Swedish pharmacist who discovered the following organic
acids: Lactic acid, Tartaric acid, Citric acid, and Oxalic acid Sources of New Drugs:
 Also one of those who discovered arsenic
 Discovered oxygen a year before Priestley.  Plant Kingdom
 Rauwolfia serpentina (Reserpine)- Tranquilizer and a
 Friedrich Serturner Hypotensive Agent
 German pharmacist who isolated morphine from opium  Digitalis lanata (Digoxin) – A cardiac glycoside
 Vinblastin and Vincristine (Taxus brevifolia / Taxus bacata)-
 Pierre Robiquet For certain types of cancer (Acute Leukemia)
 He independently isolated cocaine from opium.  Pacific Yew Tree (Paclitaxel) – for ovarian cancer

 Joseph Caventou and Joseph Pelletier  Animal sources

 They isolated quinine and cinchonine from cinchona.  Draculin was developed from vampire bat saliva to treat heart
 Also, they discovered strychnine and brucine from Nux vomica. attacks and strokes in humans.
 Endocrine glands of cattle, sheep and swine - Thyroid extract,
 Pierre Robiquet and Joseph Pelletier insulin and pituitary hormone (Replacement Therapy).
 Both isolated caffeine.  Urine of Pregnant mares – Source of Estrogens

Standardization of Drugs  Microbiological world/source

 Bacitracin - from strain of B. subtilis
Drug Standards – the scientific basis for drug products to ensure uniformity  Polymycin B - from B. polymyxa
and quality leading to the development and publication of monographs.  Tetracycline - from S. aureofaciens
 Chloramphenicol - from S. venezuelae
Pharmacopeias – the term comes from the Greek word “pharmakon” (drug)  Erythromycin - from S. erythreus
and “poiein” (to make.)  Neomycin - from S. fradiae
 Present Official standard of Purity, Strength, Quality, and Analysis of
drugs.  Biological Source
 USP  List of substances with therapeutic activity  Serums, Anti-toxins, and Vaccines (living or killed
 National Formulary  excipients microorganisms)
 EO 302 s. 2004  Law that recognizes of Philippine Pharmacopoeia  These became lifesavers since the discovery of Edward Jenner
as an official book for standard and preference of drugs in the on the smallpox vaccine in England in 1796.
Philippines.
Goal Drug
Official Compendia – contains drug monographs which assured availability  Produces the specifically the desired effect
of quality drugs and pharmaceutical products.  Administered by the most desired route (Generally orally)
 Minimal dosage and dosage frequency
Parts of Pharmacopoeia:  Has optimal onset and duration of activity
 Easily produced at low cost
 Monograph  Pharmaceutically elegant
 Articulate the quality expectations for a medicine including for its  Physically and chemically stable in various conditions of use and
identity, strength, purity, and performance. They also describe the storage
tests to validate that a medicine and its ingredients meet these criteria.  Exhibit no side effect
 Would be eliminated completely and without residual effect
 General Chapters/ General notices
 Provides broadly applicable information to industry on accepted Drug Discovery
processes, tests and methods to support product development and  Choosing a Disease – Focus is on the financial return
manufacturing for innovative, generic and biosimilar medicines.  Choosing a drug Target – Receptor, enzymes, and metabolic
processes.
 Material reference standard  Medical Folklore
 Are used in conjunction with monographs and general chapters to  Existing Drugs
verify that a medicine and its ingredients can past tests to ensure  Combinatorial Synthesis
adherence to quality requirements.  Molecular Modification
 Mechanism-based Design
The USP updates 3x a year. (November, February and June)
 Computer-aided Design
 Serendipity and Prepared Mind
Official Compendia
 Use of NMR
 Lititz Pharmacopoeia
Identifying a Bioassay
 The first American Pharmacopoeia published in 1778 at Lititz,
1. In Vitro Test – Initial bioassay that takes place outside the organism,
Pennsylvania
in an artificial environment such as a laboratory where drug activity is
 It was a 32 page booklet consisting 84 internal and 16 external
tested on isolated tissues, cells, or enzymes.
drugs and preparations
2. In Vivo Test- Subsequent bioassay by biological experiment or  To conceal the salty, bitter, offensive taste or odor of a drug
technique carried out within a living organism substance.
 To provide liquid dosage forms of substances soluble in the desired
Pre- Phase I Phase II Phase III vehicle.
clinical  To provide liquid preparations of substances that are either insoluble
Testing or unstable in the vehicle.
Years 3.5 F 1 2 3  To make minute or small dose of a drug larger enough to be picked up
Test Laborator i 20 to 80 100 to 300 1000 to with the fingers.
Populatio y and l healthy patient 3000  To provide for optimal drug action through inhalation therapy.
n animal e volunteers volunteers patient  To provide extended drug action through controlled-release design.
studies I volunteers  To provide optimal drug action from topical administration sites.
Purpose Assess N Determine Evaluate Verify  To provide for the insertion of a drug into one of the body orifice.
safety and D safety and effectivene effectivene  To provide for the placement of drugs directly into the blood stream.
biological a dosage; ss, look for ss, monitor
activity t Bioav side effects adverse Physicochemical Parameters
F reactions  Melting point
D from long-  Phase Rule
A term use  Polymorphism
Success 5,000  Particle size
Rate compound 5 enter trials  Solubility
s  Membrane permeability
evaluated  Partition coefficient
 Dissociation constant

Pre-Clinical Studies Drug Stability

 Chemical and Physical Characterization  Stability - Capability of a particular formulation in a specific container
 Pharmacology or closure system to remain within its physical, chemical,
 Pharmacokinetics microbiological, therapeutic and toxicological specifications.
 Pharmacodynamics
 Pharmaceutics  Expiration date - Limits the time during which the product may be
 Analytical studies dispensed by the pharmacist or used by the patient.
 Toxicology
 Shelf-life - Refers to the duration of time during which a drug
Human Studies preparation will remain physically, chemically, therapeutically,
Blinded Studies: toxicology and microbiology stable (possessing NLT 90% of the
 Single Blind Studies- The patient does not know or unaware of the labeled potency).
agent administered.
 Double Blind Studies- Neither the patient nor the clinician is aware of Types of Stability
the agent administered.  Chemical
- Hydrolysis
Open Label Studies: - Hydroxylation
 Parties are aware of the agents’ identities that will be administered to  Physical
them.  Microbiologic
 Therapeutic
Submission of a New Drug Application  Toxicologic
 Submitted to the FDA for review and approval after the completion of
the clinical trials and requirements have been met. Types of Stability Studies
 When the preclinical and clinical studies have proven the IND’s 1. Long term or actual
effectiveness and safety by all parameters.  Conducted under the usual / normal conditions of the
environment, transport and storage expected during product
Phase IV distribution.
 Phase 4 also known as Post Marketing Studies and manufacturing  25+/-2°C, 60+/-5%RH, 12mos.
scale-up activities take place.  It makes use of different “climatic zones” also called Global
 Scale-up – increase in the batch size from the clinical batch, Assessment of Stability of exposure:
submission batch, or to the full-scale production batch size, using the Zone 1 – Temperate
finished, marketed product. Zone 2 – Subtropical
 Product development may continue. Zone3–Hot and dry
Zone 4 – Hot and humid
Additional Applications
 ANDA or Abbreviated New Drug Application - Filed for generic 2. Accelerated
copies by competing companies following expiration of patent term  Studies designated to increase the rate of chemical or physical
protection. degradation of a drug substance or product by using
 SNDA or Supplemental New Drug Application - There are changes in exaggerated storage conditions.
synthesis, formulation, analytical standards, containers, and labeling  40.0°C,75%RH, 6mos.
of drug products.
Extemporaneous Preparations
Lead Compound  Non-aqueous liquids and solids
 A prototype chemical compound that has a fundamental desired - from a manufactured product  6 months, or not later than
biologic or pharmacologic activity. 25% of the time remaining.
Example1: Development of new generations of cephalosporin - From a USP/NF active  6 months
antibiotics.
Example2: Additional H2-Antagonists from the pioneer drug  Aqueous or water containing
Cimetidine. - From a manufactured solid form 14 days stored at cold
temperature
 Since most drugs have primary and secondary effects, taking
advantage of secondary effects leads to a drugs secondary indication.  Others  30 days
Example: Finasteride(Proscar/Atepros)
PREPARATION CATEGORY MONOGRAPH OR
Prodrugs LABEL WARNING
 A compound that requires metabolic biotransformation after Epinephrine Adrenergic drug Do not use if it is
administration to produce the desired pharmacologically active brown or contains
compound. precipitate.
Isoproterenol Adrenergic Do not use if it is
New Drug (Bronchodilator) pink to brown or
 A combination of two or more old drugs or change in usual contains a
proportions of drugs in an established combination product is precipitate.
considered new if the change alter safety and efficacy.
Paraldehyde Hypnotic Subjected to
 A change in previously approved formulation or method of oxidation to form
manufacture constitutes newness since such change can alter effects
acetic acid.
and safety of a product.
Nitroglycerin Anti-anginal Keep on original
 A proposed new use for an established drug, a new dosage regimen or
container or
schedule, a new route of administration, or a new dosage form leads to
supplemental
a drug’s status new and triggers reconsideration for safety and
container specifically
efficacy.
labeled suitable for
Nitroglycerin tablets
Dosage Form Development
to prevent loss of
Dosage Form:
potency.
 It is a finished formulation of a drug preparation designed to contain a
specific amount of a medication.
Pharmaceutical Ingredients
The Need for Dosage Forms: 1. Active ingredient or active pharmaceutical ingredient
 For protection of drug substance from the destructive influences at - Any component that is intended to furnish pharmacologic
activity or other effect in the diagnosis, cure, mitigation,
atmospheric oxygen or moisture.
 For the protection of the drug from the destructive influence of gastric treatment, or prevention of diseases or to affect the structure of
the body of a man or other animals.
acid after oral administration.
2. Inactive or excipient  Tablet excipient
- Any component other than the active ingredient in a drug  Essential components – those that impart satisfactory
product that is used as a carrier for the active ingredients of a characteristics to the formulation (diluent, binders,
medication. In addition, excipients can be used to aid the disintegrants)
process by which a product is manufactured.  Compression aids – those that impart satisfactory compression
characteristics (glidants, lubricants, and antiadherents)
Inert substances added to achieve the final dosage form  Supplementary components – those that give additional
 Acidifying agent desirable physical characteristics to the finished tablets (colors,
 Provide acidic medium for product stability flavors, sweetening agents, adsorbents)
 HNO3, HCl, CH3COOH
Flavorants
 Alkalinizing agent  Flavorants degrade due to exposure to light, temperature, oxygen,
 Provide alkaline medium for product stability water, enzymes, contaminants, and other components thereby they
 Ammonia solution, sodium borate, sodium carbonate, trolamine must be carefully selected and checked for stability.
 Correlated structures:
 Adsorbent Salty  salts
 Hold the molecules into its surface for moisture sensitive Sweet taste  organic compounds with –OH
products groups
 Cellulose, activated charcoal Bitter taste  N-containing compounds

 Aerosol propellant Carriers:

 Develops the pressure in the container and expels the product 1. Oil-soluble carriers - Soybean and other edible oils.
 DCDFM, DCTFE, TCMFM
2. Water-soluble carriers - Water, ethanol, propylene glycol, glycerin,
 Antioxidant and emulsifiers.
 Inhibits the process of oxidation for possible cause of product
deterioration 3. Dry carriers - Maltodextrin, corn syrup solids, modified starches, gum
 Butylated hydroxytoluene, sodium bisulfite, ascorbic acid arabic, salt, sugars, and whey protein.

 Antifungal agent Types:

 Prevents growth of fungi 1. Natural Flavor - Derived from fruit or fruit juice, vegetable or
 Paraben, benzoic acid, sodium benzoate vegetable juice, herb, bark, root, and leaves of plants.

 Antimicrobial preservative 2. Artificial Flavor - Not derived from natural sources.

 Prevents growth of microorganism
 Benzalkonium chloride, benzyl alcohol, chlorobutanol, Methods:
thimerosal, phenol 1. Blending
2. Overshadowing
 Buffering agent
 Resist changes in pH Sweetening Agents
 Citrates, Acetates, Phosphates  Saccharin
- 300× sweetness (by weight), E954, FDA Approved 1958
 Chelating agent - found to cause bladder tumors but by a non-DNA reactive
 Used as stabilizers for heavy metals capable of promoting mechanism
instability - Remains unmetabolized
 Edetate disodium
 Cyclamate
 Colorant - 30× sweetness (by weight), Abbott, E952, FDA Banned 1969
 Impart color for improved aesthetic appeal (can cause bladder cancer in rats), pending re-approval
 Dyes and Lakes - Safety has not been demonstrated
 Red ferric oxide, caramel, FD&C and D&C
 Aspartame
 Clarifying agent - 160–200× sweetness (by weight), NutraSweet, E951, FDA
 Used as filtering aid for the adsorbent properties Approved 1981
 Bentonite - metabolized into phenylalanine, aspartic acid, and methanol
- Because of metabolism to phenylalanine, it is discourage to use
 Emulsifying agent for person with phenylketonuria. Proper labeling shall apply.
 Promote and maintains dispersion of finely divided particles of - Because they cannot metabolize phenylalanine adequately, this
a liquid can result to hyperphenylalaninemia (mental retardation and
 Acacia, spans and tweens, SLS, Cetyl pyridinium chloride affect the fetus)

 Flavorant  Sucralose
 Imparts pleasant flavor - 600× sweetness (by weight), Tate & Lyle, E955, FDA
Approved 1998
 Humectant
 Prevents drying out of the preparation.  Acesulfame K
 Glycerin, sorbitol, propylene glycol - structurally similar to saccharin
- 130 times as sweet as sucrose
 Levigating agent - More stable than aspartame
 An intervening agent used to reduce the particle size
 Mineral oil, glycerin  Stevia
- from Stevia rebaudiana bertoni
 Ointment bases - Natural, safe, non-toxic
 Semisolid vehicle for drug substances - 30 times as sweet as sucrose

 Solvent Colorants
 An agent used to dissolve another substance  Natural
 Water, alcohol, glycerin, mineral oil, Peanut oil, Sesame oil, - Minerals, Plants, Animals
Cottonseed oil, Castor oil - Ex. Red ferric oxide, anattenes, cochineal

 Stiffening agent  Synthetic

 Agents that increase the thickness or hardness of the - William Henry Perkin accidentally discovered
preparation. mauverine/mauve on 1856, the first synthetic dye.
 Cetyl alcohol, paraffin, white wax, yellow wax. - - Contains chromophore

 Suppository base Classified into:

 A vehicle for drug substances formulated into suppositories 1. FD and C
 Cocoa butter, witepsol, wecobee, PEG mixtures 2. D and C
3. External D and C
 Surfactant
 Agents which reduces interfacial tension  Dyes - In the form of diluted solutions. Greater accuracy in
 Benzalkonium chloride, polysorbate 80, SLS measurement
 Lakes - Pigments added to liquid dyes. Commonly, they are in the
 Suspending agent form of fine dispersions or suspensions.
 Increases viscosity and reduces rate of sedimentation  FD&C YELLOW NO.5 (tartrazine) – Cause allergy in humans
 CMC, MC, bentonite, acacia  FD&C RED NO.4 (maraschino cherries) – External application and
cosmetics
 Sweetening agent  FD&C RED NO. 2 (Amaranth) - researchers in Russia reported that
 Imparts sweetness it can cause cancer in rats.
 Mannitol, saccharin, sorbitol, sucrose
Preservatives
 Examples and their concentrations:
1. Benzoic Acid - 0.1 to 0.2%
2. Sodium Benzoate - 0.1 to 0.2%
3. Alcohol - 15 to 20%
4. Phenylmercuric nitrate and acetate - 0.002 to 0.01%
5. Phenol - 0.1 to 0.5%
 6. Cresol - 0.1 to 0.5% 1.1. Convective (Pore) Transport
7. Chlorobutanol - 0.5%  Drug transport across tight (narrow) junctions
8. Benzalkonium chloride - 0.002 to 0.01% between cells or transendothelial channels of cells
9. Combination of Methylparaben and Propylparaben- 0.1 to 0.2%  Drug molecules dissolved in aqueous medium at
the absorption site move along the solvent through
Biopharmaceutics and Pharmacokinetics Considerations the pore
 Also known as paracellular transport
Routes of Administration Examples
– Inorganic and organic electrolytes up to 150 to
 Oral Route: 400MW
Advantages: – Ions of opposite charge of pore lining
- Uncomplicated – Ionized sulfonamides
- Convenient
- Safe 2. Specialized Transport System

Disadvantages: 2.1. Active Transport

- Slow drug response  type of specialized transport system where
- Irregular absorption movement of the drug molecule is against the
- Destruction of certain drugs at the GIT. concentration gradient

 Rectal Route: 2.2. Facilitated Diffusion

Advantages:  also a type of specialized transport system where
- Drugs are destroyed by GI fluids when oral route is precluded. movement of drug is not against concentration
- When patient is unconscious, or incapable of swallowing. gradient

Disadvantages: 2.3. Ion Pair Transport

- Inconvenient, frequently irregular  Strong electrolytes drugs are highly ionized or
- Difficult to predict. charged molecules, penetrate membranes poorly
Examples
 Parenteral Route – Quaternary ammonium compounds
Advantages: – Sulfonic acids
- Rapid absorption
- Doses are smaller 2.4. Pinocytosis/Endocytosis
- Used for uncooperative, unconscious patients, or those unable  engulfing vesicles
to accept oral medication. Examples
– Fats, glycerin, starch
Disadvantages: – Parasite eggs
- Strict sterility required – Vitamins A, D, E and K
- More expensive – Plastic particles, hairs and yeast cells
- Difficult to recover – Ferritin and insulin
- Requires competent trained personnel for proper administration.
Drug Distribution
a. Intravenous injection  Central Compartment
- Used when a rapid clinical response is necessary - The central compartment includes the well- perfused organs and
tissues (heart, blood, liver, brain and kidney) with which drug
b. Intra-arterial injection equilibrates rapidly.
- Used in certain special situations, to deliver a high
concentration of drug to a particular tissue.  Peripheral Compartment(s)
- The peripheral compartments include those organs which are
c. Intrathecal injection less well-perfused, and with which drug therefore equilibrates
- Given via lumbar puncture and injection into the subarachnoid more slowly.
space.
 Special Compartments
d. Intramuscular injection - These include cerebrospinal fluid (CSF) and central nervous
- Drugs may be injected into the arm (deltoid), thigh (vastus system (CNS) , the blood- brain barrier , pericardial fluid,
lateralis) or buttocks (gluteus maximus). bronchial secretions and fluid in the middle ear

e. Subcutaneous injection Metabolism

- Used for drugs like insulin, absorption is slower than IM  aka Drug Biotransformation
 Liver is the primary organ for metabolism
 Topical Application  Extrahepatic sites: lung, kidney, intestine, skin and placenta and GI
Advantages: tract
- Provides direct local effects.  The general goal of drug metabolism is to transform such compounds
into more polar (i.e., more readily excretable) water soluble products.
a. Eye
- For desired local effects. Phase I
- Phase I reactions refer to those which convert a drug to a more
b. Intravaginal polar compound by introducing or unmasking polar functional
- For infections or contraceptives groups such as -OH, -NH 2 , or - SH.
c. Intranasal Phase II
- For alleviation of local symptoms
Drug Elimination
d. Skin  The kidney is the most important organ for the excretion of drugs
- Minimal systemic exposure and/or their metabolites.
 Some compounds are also excreted via bile, sweat, saliva, exhaled air,
e. Drug patches or milk, the latter a possible source of unwanted exposure in nursing
- (drug enters systemic circulation by zero order kinetics – a infants.
constant amount of drug enters the circulation per unit time).
Bioavailability
 Inhalation  is the proportion of a drug that is delivered to its site of action in the
- Volatile anesthetics, as well as many drugs which affect
body.
pulmonary function, are administered as aerosols.
 Importance: The amount or proportion of the drug absorbed from a
formulation or dosage form.
Drug Absorption
 Biological Factors  The rate or speed at which the drug was absorbed.
- Membrane permeability  The duration of the drug’s presence in the biological fluid or tissue as
- Blood flow correlated to patient response.
- Gastric emptying time  The relationship between drug blood levels and therapeutic
- Drug binding effectiveness or toxic effects.

 Physicochemical Factors Parameters for Assessment

- pH partition  Peak height concentration – is the maximum drug concentration
- Ion Trapping observed in the blood plasma or serum following a dose of the drug
(cmax)
Transport Mechanism
1. Passive Diffusion  Time of the peak concentration – the time required to achieve the
 Describe the passage of drug molecules through a membrane maximum level of drug in the blood (Tmax)
that does not actively participate in the process.
 The absorption process is driven by the concentration gradient  Area under the curved – a representative of the total amount of drug
existing across the membrane. absorbed into the circulation following the administration of a single
 It is described by the Fick’s first law. dose of that drug (AUC)
Examples:
Weak organic acids
Weak organic bases
Organic nonelectrolytes (alcohol, urea)
Cardiac glycosides
Bioequivalence Labeling
Pharmaceutical equivalents – drug products that contain identical amounts  Label – means a display of written, printed or graphic matter upon the
of identical active ingredient immediate container, or attached to or accompanying any
pharmaceutical specialties.
Biological equivalents – pharmaceutical equivalents which when  Labeling - means all labels and other written, printed, or graphic
administered to the same individual, in the same dosage regimen, will result matter upon any article or on any of its container or wrappers
in comparable bioavailability. accompanying such articles.
 Inner label – label on or affixed to an immediate container of a drug.
Pharmaceutical alternatives – drug products that contain identical  Outer label – labels on or affixed to the outside package of a drug.
therapeutic moiety but not necessarily same amount or dose or form.  Product’s package insert – a written, full disclosure and balanced
presentation of the positive as well as the negative aspects of the drug
Therapeutic equivalents - drug products that are pharmaceutical product to enable the prescriber to utilize the drug most safely and
equivalents and can be expected to give the same therapeutic effect when effectively.
administered to the patient under the conditions specified in the labeling.
Storage Conditions
Dosage Regimen  Cold: between 2 to 8°C
 Usual dose  Freezer: (-20) to (-10°C)
- the amount that may be expected to produce, in adults, the  Cool: between 8 and 15° C
medicinal effect for which it is intended  Room temperature: 15 and 30°C
 Warm: between 30 and 40°C
 Initial dose  Excessive heat: any temperature above 40°C
- also the priming or loading dose, is the amount required to
attain the desired concentration of the drug in the blood or Solid Dosage Forms
tissues.
Powders
 Pediatric dose  “Powder" refers to a dosage formulation that is solid in physical state
- dose administered to children but the formulation may be composed of only the active drug or may
be a mixture of the active drug and other ingredients.
 Prophylactic dose  Advantages: each dose can contain a different amount of active drug.
- the amount administered to a patient before exposure or  can be administered easily to infants and young children who cannot
contraction of the illness swallow tablets or capsules
 drug will have a rapid onset of action since disintegration is not
 Therapeutic dose required
- the amount which is administered to a patient after the exposure  drugs tend to most stable as a solid
or contraction of an illness  can be made into many different dosage formulations

 Usual dosage range Powder Fineness

- amounts of drug that may be prescribed within the work of
usual medical practice Powder Definition
Very coarse (No. 8) All particles pass through a No. 8
Labeling, Packaging and Storage sieve and not more than 20% pass
Container - a device that holds a drug and is, or may be, in direct contact through a No. 60 sieve.
with the drug. The immediate container is that which is in direct contact with Coarse (No. 20) All particles pass through a No.
the product. The closure is part of the container. 20 sieve and not more than 40%
pass through a No. 60 sieve.
Types of Container: Moderately Coarse (No. 40) All particles pass through a No.
 Well-closed – it protects the contents from extraneous solids and from 40 sieve and not more than 40%
loss of the drug under ordinary conditions of handling, shipment, pass through a No. 80 sieve.
storage and distribution. Fine (No. 60) All particles pass through a No.
60 sieve and not more than 40%
 Tight container – protects the contents from contamination by pass through a No. 100 sieve.
extraneous liquids, solids or vapors from loss of the drug and from Very fine (No. 80) All particles pass through a No.
efflorescence, deliquescence or shipment, storage and distribution. 80 sieve. There is no limit to
greater fineness.
 Hermetic container – container that is impervious to air or any other
gas under the ordinary or customary conditions of handling, shipment, Communition Methods
storage and distribution  Trituration or Communition
- Grinding a drug in a mortar to reduce its particle size
 Light-resistant containers – containers that prevent photochemical  FitzMill comminuting machine
decomposition of substances that are photosensitive. - example of mill used in large scale grinding and pulverization
 Levigation
 Single dose container – in which the quantity of the sterile drug - reduces the particle size by triturating it in a mortar or
contained is intended as single dose and which cannot be resealed spatulating it on an ointment slab or pad with a small amount of
once opened. a liquid in which the solid is not soluble.
Example of levigating agents:
 Multiple-dose container – a hermetic container which permits 1. Mineral oil
withdrawal of successive portions of the contents without changing 2. Glycerin
the strength or endangering the quality or purity of the remaining
portions. Blending Methods
 Spatulation
 Single –unit container – one that is designed to hold a quantity of - mixing is with the aid of a spatula; not suitable for large
drug intended for administration of a single dose. quantities of powders; suitable for powders capable of forming
eutectic mixtures.
 Multiple-unit – contain one or more dose of the medication.
 Trituration
 Single use package – a unit dose package at the time a prescribing - for comminution and mixing as well; light trituration ensures
physician orders that particular amount of the drug for a specific light diffusible powders while heavy trituration results to fine
patient. and dense powders.

Special Types of Container  Geometric Trituration or Dilution

 Child-safety container – CR container, one that is difficult for - for potent substance mixed with large amounts of diluents.
children under 5 years of age to open or to obtain harmful amount of
the contents  Sifting
- using sifters to produce light, fluffy powders
 Tamper-resistant container – one having indicators or barriers to
entry which, if breached or missing, can reasonably be expected to  Tumbling
provide visible evidence to consumers that tampering has occurred. - large containers which rotates generally by a motorized process

Official Glass Types Bulk Powders

Type I: highly resistant-borosilicate glass  Dusting Powders
Type II: treated-soda lime glass - fine medicinal (bulk) powders intended to be dusted on the skin
Type III: soda-lime glass by means of sifter-top containers.
Type IV: general purpose soda-lime glass - Bentonite, kaolin, kieselguhr, magnesium carbonate, starch, and
talc
Plastic Containers
 Douche Powders
Advantage Disadvantages - They are most commonly intended for vaginal use although
they may be formulated for nasal, otic or ophthalmic use.
 Lightness of weight  Permeability
 Versatility  Leaching
 Insufflations
 Convenience  Sorption
- are extremely fine powders to be introduced into body cavities.
 For unit-dose delivery  Alteration of container
 Transmission of light  Powder Sprays
- In contrast to dusting powders, powders dispensed under
pressure will deliver targeted and uniform application at the
desired site.
Divide Powders  Kapseal
 Chartulae/Powder Papers (Chart) - This is a distinctive looking capsule because of the sealing with
- Single doses of powdered medicinals individually wrapped in a colored band of gelatin. This is used by Parke-Davis.
cellophane, metallic foil, or paper.
Types of Powder Papers:  Coni-Snap
 Vegetable Parchment - The rim of the capsule body is not straight but tapered slightly.
 White bond paper This eliminates splitting of the joined capsule.
 Glassine
 Waxed Soft Gelatin Capsules
 Also referred to as “Pearls” or SGC
Granules  Oblong, elliptical, or spherical in shape, may be used to contain
 Are particles ranging in size from about 4 to 12-sieve size range. liquids, suspensions, pasty materials, dry powders, or pelletized
 The most popular compounded granulation is the effervescent powder materials.
(sometimes called effervescent salts).
Substances to be Filled in SGC
Methods of Preparing Granules:  Water immiscible, volatile and nonvolatile liquids such as vegetable
1. Dry Method and aromatic oils, aromatic and aliphatic hydrocarbons, chlorinated
o First Method- The dry powder is passed through a roll hydrocarbons, ethers, esters, alcohol and organic acids.
compactor (also called roll press or roller compactor) and then  Water miscible, nonvolatile liquids such as polyethylene glycols, and
through a granulating machine. nonionic surface-active agents as polysorbate.
 Water miscible and relatively nonvolatile compounds, as propylene
o Second Method- “Slugging” or the compression of powder glycol and isopropyl alcohol, depending upon factor as concentration
mixture into larger tablets or slugs on compressing machine used and packaging conditions.
under 8,000 to 12,000 pounds of pressure.
Methods of Preparing SGC:
2. Wet Method 1. Plate Process (the oldest method)
o First Method- moistening of the powder mixture and passing of 2. Rotary Die Process
the resulting paste through a screen of the mesh size to produce 3. Reciprocating Die Process
the desired size of granules. The granules are placed on drying
trays and dried by air or under heat. The granules are Microencapsulation
periodically moved on the drying tray to prevent adhesion into a  A process by which solids, liquids, or even gases may be enclosed in
larger mass. microscopic particles by formation of thin coatings of wall material
around the substance. Gelatin is a common wall-forming material.
o Second Method- “Fluid-bed Granulation” or fluid bed This process has originated in the late 1930s.
processing is done by placing the particles in a conical piece of
equipment and vigorously dispersed and suspended while a Test for Capsules
liquid excipient is sprayed on them and the product is dried,  Disintegration Test
forming granules or pellets of defines particle size. - The capsules are place in a basket rack assembly which is
immersed 30 times per minute into a 37 degree celsius
Capsules controlled fluid. To satisfy the test, the capsules disintegrate
 Are solid dosage forms in which one or more medicinal or inert completely into a soft mass having no palpably firm core and
substances are enclosed within a small gelatin shells. only some fragments of the gelatin shell remain.
 Empty capsule shells are made of gelatin, sugar, and water.
 Can be clear, colorless, tasteless, and colored with various FD&C and  Dissolution Test
D&C dyes. - The capsules are place in a vessel with a dissolution medium
(37 +/- 0.5 degree celsius temperature). Then a stirrer is rotated
Advantages of Capsules at a specified speed. Then, it is withdrawn for chemical analysis
 Conveniently carried of the proportion of drug dissolved.
 Readily identified
 No need to use spoons or measuring devices  Weight Variation and Content Uniformity
 Accurate amount - The USP requires adherence to standards for weight variation
 Most capsules, like tablets, are tasteless when swallowed. and content uniformity for capsules to assure the accuracy of
 Available to many dosage strengths dosage units.
 Manufacturers’ name and product code number could emboss or
imprint on the surface to be easily identified.  Stability Testing
- This is to determine the intrinsic stability of the active drug
Gelatin molecule and the influence of environmental factors such as
1. Pork Skin Gelatin temperature, humidity, light, formulative components, and the
- contributes to the plasticity and clarity to the blend, thereby container.
reducing haze or cloudiness of the capsules.
Tablets
2. Calf Bone Gelatin  Solid dosage forms contain drug with or without suitable diluents
- gives tough and firm film but tends to be hazy and brittle by prepared by Compression or Molding
itself.  Are solid dosage forms of medicinal substances usually prepared with
the aid of suitable pharmaceutical adjuncts.
Hard Gelatin Capsules
 Aka Dry Filled Capsules (DFC) or Telescoping Capsules Characteristics of Ideal Tablets
 When humidity is low, the capsules become brittle; if humidity is  Free of defects
high, the capsules become flaccid and shapeless.  Strong enough to withstand the mechanical stresses of production
 Empty capsules are numbered from 000 (the largest size that can be  Chemically and physically stable over time
swallowed) to 5 (the smallest size)  Capable of releasing medicinal agents in a predictable and
 Consist of body and Cap. reproducible manner
Limitations of Capsules as Dosage Forms Tablet Excipients
 Not used for extremely soluble salts such as KI, KBr, or Ammonium  Essential Components
chloride due to sudden release of the drug in the GIT, which may be 1. Diluents
irritating.
 are fillers designed to make up the required bulk of the tablet
 Not used for highly efflorescent or deliquescent material.
when the drug dosage amount is inadequate.
 Common diluents include kaolin, lactose, mannitol, starch,
Method of Production of Hard Gelatin Capsule
microcrystalline cellulose, powdered sugar, and calcium
 The “pin method” is adapted with use of completely automatic
phosphate.
machines consisting of dipping, spinning, drying, stripping, and
joining the capsules. The entire process takes about 45 minutes.
2. Binders and Adhesives
 are added in either dry or liquid form to promote granulation or
Preparation of Filling Hard Gelatin Capsules
to promote cohesive compacts during direct compression.
 “Punch Method”
- Using a spatula, the powder mixture is formed into a cake
having a depth of approximately 0ne-fourt to one-third the Examples:
 10%-20% aqueous preparation of cornstarch
length of the capsule body. The capsule body is held between
the thumb and forefinger and punch vertically into the powder  25%-50% solution of glucose
 Molasses
cake repeatedly until filled. This is not done with bare hands.
 various natural gums
 cellulose derivatives
 “Capsule Filling Machines”
 Gelatins
- Some capsule filling machines are hand- operated that are used
 Povidone
by pharmacists on regular preparations. It can produce 200 to
2000 capsules per hour. Some capsule filling machines are
more complicated and are used by manufacturing firms. 3. Disintegrants
 These are added to tablet formulations to facilitate
Specially Designes Capsules disintegration when the tablet contacts water in the
 Spansule gastrointestinal tract.
- Ends of both bodies and cap are highly tapered/narrowed. Used
by Smith Kline Beecham. Examples:
 cornstarch and potato starch
 Pulvules  starch derivatives
- End of the body- producing peg is tapered but the cap- making  cellulose derivatives
peg is rounded. Used by Eli Lilly.  clays and cation exchange resins.
 Compression Aids  Wet granulation
1. Lubricants  This method has more operational manipulations, and is more
 reduce the friction that occurs between the walls of the tablet time-consuming than the other methods. The wet granulation
and the walls of the die cavity when the tablet is ejected. Talc, method is not suitable for drugs which are thermolabile or
magnesium stearate and calcium stearate are commonly used. hydrolysable by the presence of water in the liquid binder.

2. Anti-adherents  Dry granulation

 reduce sticking, or adhesion, of the tablet granulation or powder  The ingredients in the formulation are intimately mixed and
to the faces of the punches or the die walls. precompressed on heavy duty tablet machines. The slug which
is formed is ground to a uniform size and compressed into the
3. Glidants finished tablet.
 promote the flow of the tablet granulation or powder by
reducing friction among particles Processing Problems
1. Capping is the partial or complete separation of the top or bottom
 Supplementary Components crown from the main body of the tablet.
 Colorants
 Flavoring Agents 2. Lamination is separation of a tablet into two or more distinct layers.
 Sweetener
 Adsorbents 3. Picking is removal of the surface material of a tablet by a punch.

Tabletting Machine 4. Sticking is adhesion of tablet material to a die wall.

 Hopper - For storing the granulation material for compression.
 Feed frame/Feed Shoe - For distributing the granulation material into 5. Mottling is unequal color distribution.
the die cavities.
 Die Cavities - For controlling the size and shape of the tablets. 6. Peeling is the large amounts of film flaking from the tablet surface.
 Punches (Upper and Lower) - For compacting the granulation
material within the die cavities. 7. Orange peel effect is the roughness of the tablet surface due to failure
 Cams – For guiding the punches. of the spray droplets to coalesce.

Per oral Solid Dosage Form Ready for Administration 8. Bridging is the filling-in of the score line or indented logo.
 Compressed tablets
- are formed by single compression and have no special coating, 9. Tablet erosion is the disfiguration of the core tablet.
they are made from powdered, crystalline, or granular materials,
alone or in combination with excipient such as binders, Tablet Evaluation
disintegrants, diluents, and colorants. 1. Weight variation test
2. Content Uniformity
 Multiple compressed tablets 3. Tablet thickness
- Layered tablets are prepared by compressing a tablet 4. Tablet hardness and friability
granulation around a previously compressed granulation. 5. Tablet disintegration
- The operation is repeated to produce multiple layers. 6. Tablet dissolution

 Compression-coated, or dry-coated, tablets Liquid Dosage Forms

- compresses an outer shell around the tablets.
- thinner, more uniform coating than sugar-coating, and it can be Solutions
used safely with drugs that are sensitive to moisture.  Liquid preparations that contain one or more chemical substances
dissolved in a suitable solvent or mixture of mutually miscible
 Sugar and chocolate coated tablets solvents.
- are compressed tablets that are coated for various reasons. The  Advantages:
coating may be added to protect the drug from air and humidity, 1. Completely homogenous doses
to provide a barrier to a drug's objectionable taste or smell, or to 2. Immediate availability for absorption and distribution
improve the appearance of the tablet. 3. Provides a flexible dosage form

 Film-coated tablets Classification

- are compressed tablets that are coated with a thin layer of a  According to route or site of application
water-insoluble or water- soluble polymer. - Otic
- Oral
 Gelatin-coated tablets - Ophthalmic
- capsule-shaped compressed tablet - Topical
- Coating facilitates swallowing, tamper-evident design
 According to solvent used
 Enteric coated - Aqueous and non-aqueous
- Modified-release tablets
- intended to pass through the stomach intact to disintegrate and According to route or site of application
release their content for absorption along the intestines  Otic Solutions
- intended for instillation in the outer ear, are aqueous, or they are
 Buccal and Sublingual Tablets solutions prepared with glycerin or other solvents and
- Flat and oval tablets intended to be dissolve in the buccal pouch dispersing agents.
or beneath the tongue Examples:
– Antipyrine and Benzocaine Otic Solution
 Chewable tablets – Neomycin , Polymyxin B Sulfates And Hydrocortisone Otic
- disintegrate smoothly and rapidly when chewed or allowed to Solutions
dissolve in the mouth.
- These tablets contain specially colored and flavored mannitol  Oral Solutions
and yield a creamy base - are liquid preparations, intended for oral administration, that
contain one or more substances with or without flavoring,
 Effervescent Tablets sweetening, or coloring agents dissolved in water or co-solvent
- compressing granular effervescent salts or other materials that water mixtures.
release carbon dioxide gas when they come into contact with
water.  Ophthalmic Solutions
- sterile preparation to be used on the eyes.
 Molded Tablets - Ophthalmic drops should be clear and practically free from
- Tablets that are soft and soluble and rapidly dissolves particles when examined under suitable conditions of visibility.

 Tablet Triturates  Topical Solutions

- Compressed or molded, small, cylindrical containing small - are solutions, usually aqueous but often containing other
amount of potent drugs solvents such as alcohol and polyols, intended for topical
- Using sucrose or lactose application to the skin, or as in the case of Lidocaine Oral
Topical Solution, to the oral mucosal surface.
 Immediate-release tablets - The term “lotion” is applied to solutions or suspensions applied
- Designed to disintegrate and release their medication with no topically.
special rate controlling features
 Aqueous Solutions
 Instantly Disintegrating or dissolving tablets - Solutions that contain water as the solvent.
- RDTs dissolve in the mouth within 1 minute
- Prepared into lyophilized foam mixture and compression  Non-aqueous solutions
- Solutions that contain a solvent other than water. Ether,
 Extended-release Tablets benzene, petrol, carbon tetrachloride are some common
- These are designed to release the drug in the predetermined solvents.
time.
Composition of solutions
Methods of Preparing Compressed Tablets  Solute (smallest amount)
 Direct compression
 Powders must possess free flowing as well as cohesive  Solvent (Larger amounts, can dissolve the solute, nontoxic, safe for
properties that enable them to be compressed directly in a tablet ingestion or topical application, aesthetically acceptable)
machine without need of either wet or dry granulation.
 Additives (Colorants, flavorants, preservatives or buffering agents)
 Example is KCl.
Concentrated and Diluted Solutions  Ion Exchange - The ion exchange process percolates water through
 The solution that has a greater proportion of solute is said to be more bead-like spherical resin materials. Ions in the water are exchanged for
concentrated than the other that has a lesser proportion. other ions fixed to the beads.
 If the proportion of solute is less, the solution is said to be dilute.
Advantages Disadvantages
Solubility  Removes dissolved  Does not effectively
 the expression of the quantity of a drug that can be maintained in inorganics remove particles,
solution in a given solvent at a given temperature and pressure. effectively. pyrogens or bacteria.
 Regenerable  DI beds can generate
 It is usually expressed as the number of milliliters of solvent required  Relatively resin particles and
to dissolve 1 gram of the drug. inexpensive initial culture bacteria.
capital investment  High operating costs
Descriptive Team Parts of Solvent Required for 1 over long-term.
Part of Solute
Very soluble <1  Reverse Osmosis - In water purification systems, hydraulic pressure
Freely soluble 1-10 is applied to the concentrated solution to counteract the osmotic
Soluble 10-30 pressure. Pure water is driven from the concentrated solution and
Sparingly soluble 30-100 collected downstream of the membrane.
Slightly soluble 100-1,000
Very slightly soluble 1,000-10,000 Advantages Disadvantages
Practically insoluble >10,000  Effectively removes  Flow rates are
all types of usually limited to a
Saturated and Supersaturated solutions contaminants to some certain gallons/day
 Saturated solution is one that contains the maximum amount of extent (particles, rating.
solute that the solvent will accommodate at room temperature and pyrogens,
pressure. microorganisms,
colloids and
 Supersaturated solution is one that contains a larger amount of dissolved inorganics)
solute than the solvent can normally accommodate at that temperature  Requires minimal
and pressure. maintenance.

Factors affecting solubility c. Water for injection

1. Temperature -  solubility with an  in temperature - is water purified by distillation or by reverse osmosis, free from
pyrogen.
2. Pressure -  in pressure =  solubility of a gas in a liquid
d. Sterile water for injection
3. pH of the solution - sterilized by autoclaving in sealed containers immediately
weak bases – not very soluble in water but soluble in dilute acid (within 4-6 hours of collection) to prevent the development of
solution bacteria from which pyrogens are derived.
weak acids – form water soluble salts in basic solution
e. Water for injection free from dissolved gases
4. Particle size - The larger particles are generally less soluble. - water must be free from dissolved carbon dioxide and other
dissolved air.
5. Physical agitation – more rapid dissolution
f. Bacteriostatic water for injection
6. Nature of the solute - "like dissolves like." - Sterile water for injection containing one or more suitable
antimicrobial agents.
Nature of solute and solvent
g. Sterile water for irrigation
Solute Polar Solvent Non-Polar Solvent - sterile, distilled, nonpyrogenic water for injection intended only
Polar Soluble Insoluble for sterile irrigation, washing, rinsing and dilution purposes.
Non-Polar Insoluble Soluble
Ionic Soluble Insoluble 2. Alcohol
 considered the primary solvent for many organic compounds
General Considerations  94.9 – 96% ethanol by volume
 Organic compounds increasing in molecular weights reduces its  Miscible with water, preserving action
solubility in polar solvents  Alcohol content limits:
 Branched chains are more soluble than straight chain compounds  Under 6 y/o - 0.5%
 6 to 12 y/o - 5%
Soluble Insoluble  Over 12 and adults - 10%
nitrates, chlorates, acetates, Hydroxides and oxides
chlorates and lactates 3. Diluted Alcohol
Sulfates, sulfites and thiosulfates Phosphates, carbonates, silicates,  Mixture of equal volumes alcohol and water
borates and hypochlorites  Frequently, combination of ethanol and water (Hydro-alcoholic
Chlorides, bromides, iodides mixture) allows easier dissolution of both lipophilic and hydrophilic
Ammonium and quaternary molecules.
ammonium salts
Salts of monovalent cations 4. Ethyl Rubbing Alcohol

Solvents
1. Water

Types of Water:
a. Potable water
- Water that is fit to drink.
- Unsuitable for certain pharmaceutical purposes
o Hard water – with soluble salts of Ca and Mg  70% of ethanol, additives
o Soft water – treated with lime or ammonia  volatile, flammable
 Rubefacient, germicide, antiseptic, vehicle for topical preparation
b. Purified water
- Clear, colorless, odorless and neutral (pH 5 – 7) 5. Isopropyl Rubbing Alcohol

Preparation of Purified Water:

 Distillation - Water is first heated to boiling. Then the water vapor
rises to a condenser where cooling water lowers the temperature so the
vapor is condensed, collected and stored.

Advantages Disadvantages
 Removes a broad  Some contaminants
range of can be carried into  70% isopropyl
contaminants the condensate  External application as rubefacient and soothing rub and as a vehicle
 Reusable  Requires careful for topical products
maintenance to  91% is for diabetic patients in preparing needles and syringes for
ensure purity hypodermic injections of insulin and for disinfecting the skin.
 Consumes large
amounts of energy
 System usually takes
a large space on
counter
6. Glycerin, Glycerine, Glycerol Syrups
 These are concentrated aqueous preparations of sugar-substitute with
or without added flavoring agents and medicinal substances.

Additives:
 Polyols, such as glycerin or sorbitol, may be added to retard
crystallization of sucrose or to increase the solubility of added
 Clear, syrupy liquid, sweet taste ingredients.
 a simple polyol (sugar alcohol) compound.  Alcohol often is included as a preservative and also as a solvent
 Miscible with water and alcohol for flavors.
 Viscous, preservative action  Further resistance to microbial attack can be enhanced by
incorporating antimicrobial agents.
7. Propylene Glycol
Syrups
 Medicinal syrups are those to which therapeutic compounds have
been added (e.g. Guaifenesin Syrup)

 Non-medicated or flavored vehicles are syrups containing flavoring

agents but not medicinal substances.

 Flavoring syrups are syrups containing pleasantly flavored

 1,2-propanediol or propane-1,2-diol, substances (e.g. Cherry Syrup, Acacia Syrup, etc.).
 Viscous liquid, miscible with water, acetone, chloroform and alcohol
 one of the major ingredients of the liquid used in electronic cigarettes.  Simple syrup contains only sucrose and purified water (e.g. Syrup
USP).
Other Non-polar Solvents
Advantages
 Hydrocarbons  Provides a pleasant means of administering a liquid form of
disagreeable tasting drug.
 Peanut oil - refined fixed oil from peanuts (Arachis hypogaea)  They may particularly effective in the administration of drugs to
youngster, since their pleasant taste usually dissipates any reluctance
 Sesame oil – aka til oil, edible vegetable oil derived from sesame on the part of the child to take the medicine.
seeds (Sesamum indicum)  The fact that syrups contain little or no alcohol adds to their favor
among parents.
 Corn oil – refined fixed oil obtained from the embryo of Zea mays
Preparation of Syrups
 Cottonseed oil - fixed oil from seeds of cultivated varieties of the a. Solution with heat
cotton plant (Gossypium) - The sucrose usually is added to the purified water or aqueous
solution and heated until solution is affected, then it is strained
 Mineral oil - mixture of liquid hydrocarbons from petroleum and sufficient purified water is added to make the desired
weight or volume.
Preparation of solutions
b. Agitation without heat
1. Simple solutions - This process is used in those cases where heat would cause the
- done by dissolving the solute in a suitable solvent, which may loss of valuable, volatile constituents.
contain other ingredients, which stabilize the active ingredients.
Examples: c. Addition of medicating liquid to syrup
• Calcium hydroxide topical solution USP (limewater) - This method is used in those cases in which fluidextracts,
• sodium phosphates oral solution USP tinctures, or other liquids are added to syrup to medicate it.
• strong iodine solution USP
d. Percolation
2. Solution by chemical reaction - In this procedure, purified water, or an aqueous solution, is
- is prepared by reacting two or more solutes with each other in a permitted to pass slowly through a bed of crystalline sucrose in
suitable solvent. a cylindrical percolator, thus dissolving it and forming a syrup.
Examples:
Aluminum Subacetate Topical Solution Elixirs
 defined by the USP as "clear, sweetened, hydro-alcoholic liquids
3. Solution by extraction intended for oral use.
- Drugs or pharmaceutical necessities vegetable or animal origin  alcohol content ranges from 5-40% (10-80 proof),
are often extracted with water or with water containing other Examples of medicated elixirs:
substances. – Dexamethasone elixir USP
Methods: – Phenobarbital elixir USP
Maceration  The main ingredients in elixirs are ethanol and water but glycerin,
Decoction sorbitol propylene glycol, flavoring agent, preservatives, and syrups
Percolation often are used in the preparation of the final product. The solvents are
Digestion often used to increase the solubility of the drug substance in the
Infusion dosage form.
 Elixirs containing over ten to twelve percent of alcohol are usually
 Extraction Methods self- preserving and do not required the addition of an anti-microbial
 Maceration agent for their preservative.
o is the process in which the solid ingredients are placed in  PREPARATION: Simple Solution With Agitation - and / or by the
a stoppered container with the whole of the solvent and admixture of two or more liquid ingredients.
allowed to stand for a period of at least three days, with  An elixir may contain both water- and alcohol- soluble ingredients. If
frequent agitation. The mixture is strained and the marc such is the case, the following procedure is indicated:
pressed, and the combined liquids are clarified by  Dissolve the water-soluble ingredients in part of the water.
filtration or by decantation after standing.  Add and solubilize the sucrose in the aqueous solution.
 Prepare alcoholic solution containing the other ingredients.
 Percolation  Add the aqueous phase to the alcoholic solution, filter, and
o is where the active ingredients are extracted from a make to volume with water.
macerated drug mass in a narrow cone- shaped vessel
open at both ends (percolator) through the passage of an Tincture
extracting liquid called menstruum.  are alcoholic or hydro-alcoholic solutions prepared from vegetable or
o This is the procedure used most frequently to extract chemical substances.
active ingredients in the preparation of tinctures and fluid  tinctures of potent drugs represent the activity of 10 g of the drug in
extracts. each 100 ml of the tincture; they are 10% tinctures.
 With a few exceptions, non-potent tinctures represent 20 g of the drug
 Digestion per 100 ml of tincture.
o This is a form of maceration in which gentle heat is used  Percolation is the procedure of choice when the crude drugs are
during the process of extraction. cellular in structure; plant exudates tend to become impacted in the
o It is used when moderately elevated temperature is not percolator and stop the flow so that maceration is preferred in such
objectionable. The solvent efficiency of the menstruum is preparations.
thereby increased.
Miscellaneous Solutions
 Infusion
o The process of extracting chemical compounds or flavors Aromatic Waters
from plant material in a solvent such as water, oil or  Aromatic waters, known also as medicated waters, are clear, saturated
alcohol, by allowing the material to remain suspended in aqueous solutions of volatile oil or other aromatic or volatile
the solvent over time substances.
 Examples:
 Decoction  Aromatic waters prepared from essential oils, e.g. peppermint
o the crude drug is boiled in a specified volume of water water, have been used as carminatives.
for 15 minutes it is then cooled and strained or filtered.  Chloroform water, is used in expectorants preparations.
o Suitable for extracting water-soluble and heat stable  Rose water is a perfume.
constituents.
o Typically used in preparation of Ayurvedic extracts.
Preparation of Aromatic Waters Extracts
 Distillation method  Are concentrated preparations of vegetable (or animal) drugs. Most
 The distillation method consists of placing the odoriferous extracts are prepared by percolation followed by the evaporation of all
portion of the plant or drug from which the aromatic water is to or nearly all the menstruum, yielding a powdered or ointment-like
be prepared in a suitable still with sufficient purified water and product of extracted drug in concentrated form.
then distilling most of the water. The aqueous phase, which  On a weight-for-weight basis, extracts commonly are two to six times
may require further clarification, is the product. as potent as the crude drug.
 Example: Orange flower water
Extracts are in 3 forms:
 Solution method a. Semiliquid extracts or those with syrupy consistency prepared
 In solution method the volatile substance is agitated with without the intent of removing all or even most of the menstruum.
purified water for a period of 15 minutes.
 The mixture is then set aside for at least 12 hours, to ensure b. Pilular or solid extracts of a plastic consistency prepared with nearly
saturation, before it is filtered through wetted filter paper. all of the menstruum removed.
 Example: Chloroform water
c. Powdered extracts prepared to be dry by the removal of all of the
 Alternate solution method menstruum.
 the volatile material is mixed thoroughly with 15 gm. of
purified talc. This mixture is agitated with a liter of purified Disperse System
water for 10 minutes, prior to filtration.  The term "Disperse System" refers to a system in which one substance
(The Dispersed Phase) is distributed, in discrete units, throughout a
 The talc or other inert material functions as both a filter aid and
second substance (the continuous Phase or vehicle).
a distribution agent.
 Each phase can exist in solid, liquid, or gaseous state .
 Dilution method
Components:
 An alcoholic solution of the essential oil is mixed with water
a. Dispersion Medium
and talc. The mixture is agitated; after several hours it is
- Also called “external phase”
filtered. The concentrate contains between 50 and 55 per cent
- The liquid vehicle, to which the insoluble drug is distributed.
alcohol by volume. One volume of concentrate is diluted with
39 volumes of water, producing aromatic water which contains
b. Disperse Phase
less than 1.5 per cent of alcohol.
- also called “internal phase”
 Concentrated waters, such as peppermint, dill, cinnamon, and - The undissolved or immiscible drug distributed throughout the
caraway, may be prepared as follows: Essential oil 2 ml;
liquid vehicle.
Alcohol 90% 60 ml; Talc 5 g; Water to 100 ml.
 Particles of dispersed phase vary in size
Diluted Acids - 0.1nm - 0.5 um colloidal dispersion
 The diluted acids in the USP are aqueous solutions of acids, of a
- 10 – 50 um coarse dispersion
suitable strength for internal administration or for the manufacture of - 0.5 – 10 um fine dispersion
other preparations.
 strengths of the official undiluted acids are expressed as percentages
Suspensions
in weight (w/w)
 Suspensions are heterogenous system consisting of 2 phases.
 strengths of the official diluted acids are expressed as percent in
 The continuous phase is generally liquid or semisolid & dispersed or
volume (w/v)
internal phase is particulate matter.
 EX: Diluted hydrochloric acid USP has been used in the treatment of
achlorhydria.
Advantages of Suspensions
 Suspension can improve chemical stability of certain drug.
Spirits - E.g. Procaine penicillin G
 Spirits, sometimes known as essences, are alcoholic or hydro-
alcoholic solutions of volatile substances with alcohol contents  Drug in suspension exhibits higher rate of bioavailability than other
ranging from 62-85% (124-170 proof).
dosage forms. bioavailability is in following order:
 a spirit or spirit-like preparation may be used in the formulation of - Solution > Suspension > Capsule > Compressed Tablet >
aromatic waters or other pharmaceuticals that require a distinctive
Coated tablet
flavor.
 Whisky and Brandy are prepared by distillation.
 Duration and onset of action can be controlled.
 Compound Orange Spirit, Camphor Spirit, and Compound Cardamom
- E.g. Protamine Zinc-Insulin suspension
Spirit are prepared by simple solution.
 Peppermint Spirit, USP is prepared by solution with maceration.
 Suspension can mask the unpleasant/ bitter taste of drug.
- E.g. Chloramphenicol
Non-Aqueous Solutions
Desired Features:
Liniments  Particles should settle slowly and re- dispersed readily upon shaking
 They were once called embrocations. of its container.
 Are alcoholic or oleaginous solutions or emulsions of various
 The particle size of the suspensoid should remain fairly constant
medicinal substances intended to rubbed on the skin throughout long periods of undisturbed standing.
– Hydro-alcoholic liniments
 The suspension should pour readily and evenly from its container.
– Oleaginous liniments
 Emulsion liniments or insoluble-containing liniments must have a
Additional Components of Suspensions
“Shake well.” label.
 Flocculating agents - enhance particle "dispersability"
 Are never taken internally
 Viscosity enhancers - reduce sedimentation rate in the flocculated
 Are prepared in the same manner as solutions, emulsions, or
suspension
suspensions  Preservatives - prevents the growth of microorganisms
 Stabilizers - any additive used in substance and compounds to keep
Collodions them stable, retard deterioration
 Collodions are liquid preparations containing pyroxylin (a
 Wetting agents - They are added to disperse solids in continuous
nitrocellulose) in a mixture of ethyl ether and ethanol. liquid phase.
 They are applied to the skin by means of a soft brush or other suitable
applicator and, when the ether and ethanol have evaporated, leave a
Classification of suspensions
film of pyroxylin on the surface.
 EXAMPLE: salicylic acid collodion USP , contains 10% w/v of
Based on Particle size
salicylic acid in flexible collodion USP
 Coarse suspensions are suspensions having particle sizes of
 Are prepared by dissolving 4% w/v pyroxylin in 3:1 mixture of ether
greater than about 1micron in diameter.
and alcohol.
 Colloidal suspension contains particles that is not visible to the
 FLEXIBLE COLLOIDION - Prepared by adding 2% camphor and
naked eye, the particles being 1nm to 1um in diameter. They
3% castor oil to collodion. Castor oils makes the product flexible for
can be subdivided into:
ease in skin areas that are normally moved. The camphor gives a
 Lyophilic Colloidal Suspension which form
water-proof effect.
spontaneously when agents with a high affinity for the
continuous phase are dispersed.
Glycerins
 Glycerins or glycerites are solution or mixtures of medicinal  Lyophobic Colloidal Suspension which are
thermodynamically unstable.
substances in not less than 50% by weight of glycerin.
 Glycerin is used as the sole solvent for the preparation of antipyrine
and benzocaine otic solution USP. Based on Route of Administration
 Glycerins are hygroscopic and should be stored in tightly closed
containers. Oral Suspension
 Liquid preparation containing solid particles dispersed in a liquid
vehicle, with suitable flavoring agent, intended for oral administration.
Liquid Preparations Prepared by Extraction Processes
 Some suspensions labeled as Milks or Magmas fall into this category.
Examples:
Fluidextracts
– Milk of Magnesia
 Are also known as Liquid Extracts
 Are preparation containing plant matter, containing alcohol as solvent, – Bentonite Magma
or preservative, or both.
 Each mL contains 1 g of crude material it represents.
EXAMPLES:
Cascara Sagrada Fluidextract
Garlic Fluidextract
Licorice Fluidextract
Senna Fluidextract
Topical Suspensions Packaging and Storage of Suspensions
 Liquid preparation containing solid particles dispersed in a liquid 1. Should be packaged in wide mouth containers having adequate air
vehicle, intended for application to the skin. space above the liquid.
2. Should be stored in tight containers protected from: freezing,
 Lotions - are generally suspensions of solid materials in an aqueous excessive heat & light
vehicle. 3. Label: "Shake Before Use" to ensure uniform distribution of solid
o Advantages: particles and thereby uniform and proper dosage.
 It may be preferred over semisolid preparations because 4. Stored in room temperature if it is dry powder (25 0C). It should be
of their non greasy character stored in the refrigerator after opening or reconstitute.
 Increased spread ability over large areas of skin
 It leaves a thin coating of medicament on the skin surface Emulsion
 a dispersed system containing at least two immiscible liquid phases.
 Gels – Sometimes called jellies. Semisolid system consisting of either The majority of conventional emulsions in pharmaceutical use have
suspension made up of small inorganic particles or large organic dispersed particles ranging in diameter from 0.1 to 100 um
molecules interpenetrated by a liquid.
o Advantages: Phases:
 As a vehicle for the presentation of water-soluble  dispersed liquid - internal or discontinuous phase
medicaments, it is ideal because of their high water  dispersion medium - external or continuous phase
content.
 Products tend to be smooth. What is the difference between Emulsion and Suspension?
 Emulsion is a combination of two immiscible liquids whereas, in a
Otic Suspensions suspension, the two components can be of any phase.
 Liquid preparations containing micronized particles intended for  The stability of emulsions can be increased by adding emulsifiers.
installation in the outer ear.  The particles in a suspension can be separated by filtering, but
particles/droplets in an emulsion cannot be separated by filtering.
Ophthalmic Suspensions
 Sterile liquid preparation containing solid particles dispersed in a Types of Emulsion
liquid vehicle intended for application to the eye.  Water-in-oil (w/o) emulsions (cannot be removed by water)
- Water is dispersed as droplets in an oil or oleaginous medium.
Based on Electrokinetic Nature of Solid Particles - Used for external preparations when emollient, lubricating, or
 Flocculated protective properties are desired.
- In flocculated suspension, formed flocs (loose aggregates) will
cause increase in sedimentation rate due to increase in size of  Oil-in-water (o/w) emulsions (washed by water)
sedimenting particles. - oils, petroleum hydrocarbons, and / or waxes are the dispersed
phase, and water or an aqueous solution is the continuous phase
 Deflocculated - Oil is dispersed as droplets in an aqueous medium.
- Deflocculation is the absence of association which occurs when - formed if the aqueous phase constitutes >45% of the total
repulsive forces between particles predominate. Particles repel weight and hydrophilic emulsifier is used
each other and remain as discrete, single particles. - O/W emulsions are used topically, orally, or parenterally.

Flocculated Deflocculated  Multiple emulsions

1. Particles forms loose 1. Particles exist as separate - o/w/o or w/o/w
aggregates and form a network entities
like structure 2. Rate of sedimentation is slow  Microemulsion
2. Rate of sedimentation is high 3. Sediment is slowly formed - appear as translucent or transparent and have droplet diameter
3. Sediment is rapidly formed 4. Sediment is very closely in the nanometer range.
4. Sediment is loosely packed and packed and a hard cake is formed - The advantage of microemulsions as dosage forms as compared
doesn’t form a hard cake 5. Sediment is difficult to to conventional emulsions is their smaller droplet size, which
5. Sediment is easy to re-disperse redisperse increases drug release, and their superior physical stability.
6. Suspension is not pleasing in 6. Suspension is pleasing in - Thermodynamically stable, optically transparent isotropic
appearance appearance mixtures of biphasic o/w system stabilized with surfactants
7. The floccules stick to the sides 7. They don’t stick to the sides of - With droplets with the size of 100Å - 1000Å
of the bottle the bottle - Use for more rapid and efficient delivery of drugs following
oral or transdermal drug delivery.
Preparation of suspension
 Decipitation Methods Factor that determine the type of emulsion
- this process is done by dispersing the finely divided powders in 1. Emulsifier
an appropriate liquid vehicle. - Some emulsifiers form either w/o or o/w emulsion, others form
- The use of surfactants is desirable to ensure uniform wetting of only one type.
the hydrophobic factors. 2. Phase ratio
- Phase present in greater concentration tends to be external
 Precipitation Methods phase
- this is performed by effecting precipitation in the liquid vehicle: 3. Order of mixing
o Organic Solvent Precipitation - The phase that is being added by portions tends to be the
o Precipitation effected by changing the pH internal phase.
o By Double Decomposition Method
Identification of Emulsion Type
Factors to consider  O/W and W/O
 Wetting of particles  Miscibility test/Drop Dilution Test
 Conductivity test/Fluorescence test
 Particle size  Dye-solubility test
- Too large or too small particles should be avoided. Larger
particles will settle faster at the bottom of the container and too  Fluorescence Test
fine particles will easily form hard cake at the bottom of the - oils give fluorescence under UV light, while water doesn’t.
container.
- The particle size can be reduced by using mortar and pastel but  Miscibility/Dilution Test
in large-scale preparation different milling and pulverization - O/W emulsion can be diluted with water and a W/O emulsion
equipment are used. with oil. When oil is added to an O/W emulsion or water to a
W/O emulsion, the additive is not incorporated into the
 Sedimentation emulsion and separation is apparent.
- The velocity of sedimentation of particles in a suspension can
be determined by using the Stoke's law:  Conductivity Test
- When pair of electrodes connected to a lamp and an electrical
2
V = d (P1-P 2) g / 18n source is dipped into an O/W emulsion, the lamp lights because
of the passage of current between the two electrodes. If the
Where: lamp does not light, it is assumed that the system is W/O.
v = velocity of sedimentation
d = diameter of the particle  Dye-solubility Test
g = acceleration of gravity - The knowledge that a water soluble dye will dissolve in the
p1 = density of the particle aqueous phase of an emulsion while an oil-soluble dye will be
p2 = density of the vehicle taken up by the oil phase . Thus, if microscopic examination
h = viscosity of the vehicle shows that a water-soluble dye has been taken up by the
 Nernst and Zeta Potential continuous phase, we are dealing with an O/W emulsion. If the
- The difference in electric potential between the actual surface of dye has not stained the continuous phase, the test is repeated
the particle and the electroneutral region is referred to as Nernst using a small amount of an oil-soluble dye. Coloring of the
potential. continuous phase confirms that the emulsion is of the W/O type.
- The potential difference between the ions in the tightly bound
layer and the electroneutral region, referred to as zeta potential. Emulsifying Agents
1. Natural emulsifying agents – substances derived either form animal
 Deflocculation and flocculation or plant sources.
- Deflocculation of particles is obtained when the zeta potential is a. Those from vegetable source: Acacia, tragacanth, pectin,
higher than the critical value and the repulsive forces supersede derivatives of cellulose.
the attractive forces. b. Those from animal source: gelatin, cholesterol, wool fat
- The addition of a small amount of electrolyte reduces the zeta
potential. When this zeta potential goes below the critical value,
the attractive forces supersede the repulsive forces and
flocculation occurs.
2. Finely divided solids - substances adsorbed in the water interface to Ointment
form a coherent film.  Semi-solid preparations intended for external application to the skin or
Examples: Bentonite, veegum, magnesium hydroxide, aluminum mucous membranes.
hydroxide and magnesium trisilicate  Strong emollient effect makes it useful in dry skin conditions.
 Occlusive effect enhances penetration of active drug and improves
3. Synthetic emulsifying agents efficacy (especially in thickened, lichenified skin)
- or surface active agents, they contain both the lipophilic and  Provides a protective film on the skin (Irritant dermatitis)
hydrophilic groups.  Greasy, sticky, retains sweat (therefore, not suitable in wet weepy
- toxicity and irritancy so suitable for oral and Parenteral dermatitis, hairy areas, skin prone to folliculitis, or hot weather
administration conditions)
- High degree of compatibility  Contains no water and does not require a preservative
- Less sensitive to change pH or to addition of electrolytes
E.g. Tweens (polyethylene fatty acid ester) O/W Oleaginous Base
E.g. Span ( sorpitan fatty acid ester) W/O  On application on the skin, they have an emollient effect, protect
- D- Amphoteric surfactants against the escape of moisture, are effective as occlusive dressings,
- charge depending on the pH of the system low pH cationic and can remain on the skin for long periods without drying out, and
- high pH anionic because of the immiscibility with water are difficult to wash off.
- i.e. lecithin: used to stabilize i.v., fat emulsion  Not water washable, incorporation of water with some degree of
difficulty.
A. Anionic emulsifying agents  When powdered substances are to be incorporated into hydrocarbon
 Alkali soap: bases, liquid petrolatum (mineral oil) may be used as the levigating
- e.g. sodium, potassium and ammonium salts of fatty acids agent.
- Form o/w emulsions
- in acidic condition precipitated Fatty acid Petrolatum, USP
- For external use  It is a purified mixture of semi-solid hydrocarbons obtained from
- incompatible with polyvalent cations petroleum.
 It is an unctuous mass, varying in color from yellowish to light amber.
B. Cationic surfactants  It melts at 38°C to 60°C and may be used alone or in combination
 Quaternary ammonium compounds: with other agents as an ointment base.
- E.g. Cetyl trimethylammonium bromide (Cetrimide) and
benzalkonium chloride. White Petrolatum, USP
- Disadvantages: Toxicity and irritancy  Aka white petroleum jelly
- Incompatible with anionic surfactants, polyvalent anions  It is a purified mixture of semi-solid hydrocarbons from petroleum
- unstable at high pH that has been wholly or nearly decolorized.
- It has marked antibacterial and anti-infective properties  It is used as the same purpose as petrolatum, but because of its lighter
color, it is considered more aesthetically pleasing by some pharmacy
Semi-Solid Dosage Forms patients.
 Commercial : White Vaseline
Topical Dosage Forms
 Topical dosage form is a medication that is applied to body surfaces Yellow Ointment, USP
such as the skin or mucous membranes.  Derived from Apis mellifera
 Many topical medications are epicutaneous.  Aka simple ointment
 Topical medications may also be inhalational, such as asthma  This ointment has the following formula:
medications, or applied to the surface of tissues other than the skin, Yellow wax... 50g
such as eye drops applied to the conjunctiva, or ear drops placed in the Petrolatum... 950g
ear, or medications applied to the surface of a tooth.
 As a route of administration, Topicals are medications that contrasted White Ointment, USP
with enteral (in the digestive tract) and intravascular/intravenous  Derived from yellow ointment
(injected into the circulatory system).  Bleached and purified yellow wax
 They are intended for local effect but they may also cause systemic  This ointment differs from yellow ointment by substitution of white
effects. wax (bleached and purified yellow wax) and white petrolatum in the
formula.
Advantages of Topical Drug Delivery:
 Avoidance of first pass metabolism. Absorption Base
 Convenient and easy to apply.  Absorption bases are not easily removed from the skin.
 Avoidance of the risks and inconveniences of intravenous therapy and Two types:
of the varied conditions of absorption, like pH changes, presence of a. Those that permits the incorporation of aqueous solutions
enzymes, gastric emptying time etc. resulting in the formation of w/o emulsions.
 Achievement of efficacy with lower total daily dosage of drug by b. Those that are w/o emulsions that permit the incorporation of
continuous drug input. additional quantities of aqueous solutions.
 Avoids fluctuation in drug levels, inter- and intra-patient variations. Examples:
 Ability to easily terminate the medications, when needed.  Hydrophilic Petrolatum (Ing: Cholesterol, stearyl alc, white wax,
 A relatively large area of application in comparison with buccal or white petrolatum)
nasal cavity.  Lanolin (Anhydrous Lanolin) (Derived from wool of sheep Ovis
 Ability to deliver drug more selectively to a specific site. aries) NMT 0.5% water content
 Avoidance of gastro-intestinal incompatibility.
 Providing utilization of drugs with short biological half-life, narrow Water-Removable Base
therapeutic window.  Are o/w emulsion resembling creams
 Improving physiological and pharmacological response.  Easily washed from the skin, hence called “water washable base”.
 Improve patient compliance.  Easily washed from the skin and can absorb serous discharge.
 Provide suitability for self-medication.  Example: Hydrophilic Ointment, USP

Disadvantage of Topical Drug Delivery Water-Soluble Bases

 Skin irritation of contact dermatitis may occur due to the drug and/or  Do not contain oleaginous components
excipients.  Are completely water- washable, hence called “greaseless”.
 Poor permeability of some drug through the skin.  They soften greatly with the addition of water and usually used for
 Possibility of allergenic reactions. incorporation of solid substances.
 Can be used only for drugs which require very small plasma
concentration for action. Preparation of Ointment
 Enzyme in epidermis may denature the drugs  Incorporation Method
 Drugs of larger particle size not easy to absorb through the skin  This method involves the blending of an ingredient into the
vehicle.
Classification of Topical Drug Delivery  This is done using a glass slab and a pair of spatulas for small
volumes or using a mortar and pestle for larger volumes.
Solid Liquid Semi-solid
• Powder • Lotion • Ointment  Fusion Method
• Aerosol • Liniment • Cream  This method is used to incorporate ingredients with solid, hard
• Plaster • Solution • Paste properties such as waxes.
• Emulsion • Gel  All or some of the components of an ointment are combined by
• Suspension • Suppository being melted together and cooled with constant stirring until
• Aerosol congealed.

Creams Paste
 Emulsion of water and oil  It is a semi-solid preparations intended for application to the skin.
 Classified as oil in water (o/w) or water in oil (w/o) emulsions  They generally contains a larger proportion of solid material (25%)
 O/W creams spread easily and do not leave the skin greasy and sticky than ointment and therefore stiffer.
 W/O creams are more greasy and more emollient  Addition of powder improves porosity (breathability).
 Creams contain emulsifiers and preservatives which may cause
contact allergy Plasters
 Are solid or semi-solid adhesive masses spread on a backing of paper,
Preparation of Creams fabric, moleskin, or plastic.
 Preparation of cream involves separating the formula components into
two portions: Glycerogelatins
• Lipid portion  Are plastic masses containing gelatin, glycerin, water, and an added
• Aqueous portion medicinal substance such as Zinc Oxide.
Gels (Jellies)
 Are semisolid systems consisting of dispersions of small or large
molecules in an aqueous liquid vehicle rendered jelly-like by the
addition of an gelling agent.

Classification of Gels
1. Single Phase Gels - preparation in which the macromolecules are
uniformly distributed throughout a liquid with no apparent boundaries
between the dispersed macromolecules and the liquid.
2. Two Phase Gels- Consisting of floccules of small distinct particles.

Preparation of Gels
 Formed by dispersing the molecule in the continuous phase
 By cross-linking the dispersed molecules
 By changing the pH
 By reducing the continuous phase

Lotion
 A loosely used term that nowadays includes any liquid preparation in
which inert or active medications are suspended or dissolved.
 Most lotions are aqueous or hydro-alcoholic systems; small amounts
of alcohol are added to aid solubilization of the active ingredient(s)
and to hasten evaporation of the solvent from the skin surface.
 Most acne lotions are hydro-alcoholic which evaporate fast; they are
non-sticky and drying
 Emulsion type lotions are usually not drying, depending on the water
content (higher water and/or less oil is more drying)
 Lotions are easy to apply to large areas
 Lotions are suitable for hairy areas, skin prone to folliculitis/acne,
intertriginous areas

Factors to consider when choosing a topical preparation:

 Always consider the effect of the vehicle. An occlusive vehicle
enhances penetration of the active ingredient and improves efficacy.
 The vehicle itself may have a cooling, drying, emollient, or protective
action. It can also cause side effects by being excessively drying or
occlusive.
 Match the type of preparation with the type of lesions. For example,
avoid greasy ointments for acute weepy dermatitis.
 Match the type of preparation with the site (e.g., gel or lotion for hairy
areas).
 Consider irritation or sensitization potential. Generally, ointments and
w/o creams are less irritating, while gels are irritating. Ointments do
not contain preservatives or emulsifiers if allergy to these agents is a
concern.
  Protects and makes the most effective use of the assets of
the company
Manufacturing Level 2

Pharmacy 

“President of the Company”
General management of the business
Manufacturing Pharmacy  Active planning, direction, coordination and control of the
business
 The complete set of activities to produce a drug that comprise
production and quality control from dispensing of materials to Level 3
the release for distribution of the finished product the  “Vice Presidents, General Managers and Department
manufacture, propagation, preparation and processing of a Managers”
drug product in a large scale  Management of the major divisions / departments of the
 The making by physical, chemical, biological or any other company
procedure of any article that meets the definition of drugs Departments in a Drug Establishment (QREMMPP)
 The manipulation, sampling, testing or control procedures 1. Research Department – responsible for developing newly
applied to the final product or any other part of the process existing drug products
 The packaging, repacking or changing the container, wrapper  Library, Animal House, Pilot Plant
or label of any drug package in preparation for its distribution 2. Production Department – used for the manufacturing and
from the manufacturer to the final user production of drugs
Drug Establishment 3. Quality Control Department – considered as the “Heart and
 Any organization or company involved in the manufacture, Soul of the Manufacturing Company”
importation, repacking and/or distribution of drugs or  Used for testing and assay of drug products
medicines  Raw Material Quality Control (RMQC), In-Process
Drug Establishments are divided into three: Quality Control (IPQC), Final Product Quality
Control (FPQC)
1. Drug Manufacturer (EPBVMT)
a. Ethical manufacturers – used to produced  Green (Approved), Red (Rejected), Yellow
prescription drugs (Quarantined; further testing and assay)
b. Proprietary / Generic Manufacturers – used to 4. Marketing Department – used to promote maximum volume
produced branded and generic products of sales
c. Biologicals Manufacturers – manufactures 5. Engineering Department – responsible for locating,
vaccines, toxoid, antisera, biotechnology installing, repairing and maintaining the equipment and
d. Veterinary Products Manufacturers – facilities in a manufacturing company
manufacture drugs used for animals 6. Purchasing Department – purchase, received and
e. Medicinal Chemical Manufacturers – responsible for the inventory of supplies
manufactures active ingredients or excipients 7. Medical Department – responsible for the physical and
medical examination of employees
f. Toll / Contract Manufacturers – manufacturing
drugs for the other company 8. Warehouse Division – used as storage for all the supplies,
raw materials, in-process raw materials, and finished
 INTERPHIL – largest toll / contract
products used to manufacture the drugs
manufacturing company in the
Philippines Production Control Sections
2. Drug Importer or Exporter or Distributor  Purchasing
 Imports or exports raw materials, active ingredients or  Inventory Control
finished products for its own use or for wholesale distribution  Planning and Scheduling
on whole sale basis Warehouse Division Sections
3. Drug Trader
 Raw Materials Section
 Registered owner of the drug product but subcontracts toll
o Quarantined Area
manufacture of such products to a licensed manufacturer
o Approved for Use Area
 May also engage in distribution and or marketing of products
o Rejected Area
Organization  In-processed Section
 A mechanism for determining and assigning duties to people  Finished Products Section
on order to work effectively  Returned Goods Section
Basic Organization (5M)  Dispensing Section
 Combination of manpower, money, machines, materials, and Research and Product Development
methods so coordinated to fulfill an economic objective  Chemical Research
Basic Elements of Organization (3D)  Biological Research
 Division on responsibility  Analytical Research
 Delegation of authority Three Stages for Research
 Determination of the interrelationship among the functions of 1. Preliminary – market search, literature review, patient
each of the components of the organizational plan search
Basic Tools of Organization 2. Applied Research – chemical studies, development of
 Organizational Planning (Organizational Chart) chemical process
3. Clinical Research Stage – manufacturing requirements,
 Position Description (Job Description)
costing, product control, patent application
 Organizational Manual (Management Guide)
Current Good Manufacturing Practices (cGMP)
Levels of Top Management
Level 1  Chapter 21 of the Code of Federal Regulations Part 211
 Were first promulgated by the US Food and Drug
 “board of Trustees”
Administration (FDA) in 1963; and finalized in 1979
1
  WHO 2007 VII. Contract manufacture and analysis
 System of quality assurance aimed at ensuring that products VIII. Complaints and product recall
are consistently manufactured to a quality appropriate for IX. Self-inspection
intended use and is concerned with manufacturing and Container – device that holds a drug and is or may be in direct
quality control process and procedures contact with the drug
Philippine GMP Regulation Classifications:
AO43 s. 1999 – adoption of the first edition of the current GMP 1. According to the Contact in Drug Product
guidelines by FDA (Amendment of AO 221) a. Primary container or Immediate Container – has
AO2012-0008 – adoption and implementation of the PIC/s GMP direct contact with the drug product (Cap bottle and
as the standard on the manufacturer Cap liner)
 PIC – Pharmaceutical Inspection Convention b. Secondary container – does not have a direct
contact with the drug product but with the primary
 PICS – Pharmaceutical Inspection Co-operation
container (Carton and Boxes)
Scheme
2. According to the Ability to Protect the Drug Product
FDA MC 2012 – Philippine FDA mandated all drug manufacturers
a. Well-closed Container – protects against
to ensure strict and full compliance to the newly adopted PICS
extraneous solids and liquids, loss of drug under
Drug Discovery ordinary conditions of handling, shipment, storage
and distribution
b. Tight Container – protects from extraneous solids,
liquids, or vapors, from loss of drug and from
efflorescence, deliquescence or evaporation
c. Hermetic Container – impervious to air or any
other gases under ordinary conditions of handling,
shipment, storage and distribution, generally sterile
(vials)
d. Light Resistant Container – protects the contents
from photochemical deterioration amber, opaque,
blue
3. According to the Quantity Held
a. Single-unit
 Designed to hold a quantity of drug
intended for administration as a single
dose
 Sterility is not assured after opening
 Ampules
New Chemical Entity  Organic synthesis and Molecular b. Multiple-unit – contains more than a single dose
modification of the medication (Vials)
Pre-clinical Studies  test the safety and effectiveness of drugs in Materials Used in Packaging
animals or microbial assay 1. Glass
Submit INDA to FDA to proceed to Clinical trial  Fragile
Clinical Trials (humans)  Resistant to leaching and sorption
 Leaching – phenomenon where the container goes to
 Phase 1 – for safety of the drugs (20-100)
the drug product
 Phase 2 – for effectiveness of the drug (100-500)
 Sorption – the drugs product is absorbed by the
 Phase 3 – safety and effectiveness (500-5000)
container
 Phase 4 – Post Marketing Surveillance (Long Term and
 Type I – Highly Resistant Borosilicate Glass
Long Term ADR)
 Type II – Treated Soda Lime Glass
After clinical trial is the NDA, after approval, the drug is ready for
 Type III – Soda Lime Glass
sale
 NP – General Purpose Soda Lime Glass
10 to 20 years for a successful clinical trial to be conducted  PG Test – Powdered Glass Test
Abbreviated New Drug Application (ANDA) – filed for generic o Performed in ground / powdered glass to
copies by competing companies following expiration of patent term expose internal surface
protection o Tests the leaching potential of the glass
Supplemental New Drug Application (SNDA) – there are o Alkali titrated with 0.02N sulfuric acid
changes in synthesis, formulation, analytical standards,  WA Test – Water Attack Test
containers, and labelling of drug products o Measures the alkali release of the glass
AO43 s. 1999 o Exposure of the glass with sulfur dioxide at
121°C
 Part of quality assurance which ensures that medicinal
products are consistently produced and controlled to the Type General Uses Test
quality standards appropriate to their intended use description
I HRBSG For parenteral PG Test
Chapters of PIC/s GMP 2009
II TSLG For parenteral WA Test
I. Quality management
III SLG For parenteral PG Test
II. Personnel
III. Premise and equipment NP (Non- GPSLG Other products PG Test
parenteral) except parenteral
IV. Documentation
V. Production
VI. Quality control 2. Plastic

2
 Does not apply to a single material but rather to a vast  Non-potent  Potent
number of materials each developed to have desired features  Block and divide  Geometric dilution
 Advantage: Lightweight, flexibility, resistance to impact  Not individual dose  Individual dose
 Disadvantage: Permeability, leaching, sorption, transmission  Wide mouth plastic / glass o Bond
container or sifter top or o Glassine
of light, alteration of container upon storage
aerosol container o Vegetable
 Two types: parchment
o Thermoplastic – squeezy o Waxed
o Thermoset – firm and rigid
Plastic Materials Hygroscopic – absorbs moisture, but does not dissolve
Polyethylene (PE)  Cannot be autoclave Deliquescent – absorbs moisture and eventually dissolves
 Low density – droppers and Efflorescent – releases water of crystallization
sprays
 Moderate density – most Effervescent – releases carbon dioxide gas in water
common Comminution – particle size reduction
 High density – solid oral
 Trituration, Pulverization by Intervention, Levigation,
preparations
Milling
Polyethylene terephthalate  For beverages
 Milling – for large scale comminution process
(PET)  Amorphous PET glycol
(APETG) Principle Means of Milling:
 PET glycol (PETG) 1. Cutting / Shearing Mill (Cutting) – used for tough and fibrous
 Have transparency and luster materials
Polypropylene (PP)  Autoclavable 2. End Runner Mill (Compression)
Polyvinylchloride (PVC)  Rigid and good clarity 3. Hammer Mill, Vibration Mill (Impact)
 Blister packaging 4. Ball Mill, Pin Mill, Fluid Energy Mill (Impact and Attrition)
5. Roller Mill (Attrition and Compression) – typically used for
Safety Packaging ointments

1. Child resistant container – one that is difficult for most Blending / Mixing of Powders
children under 5 years of age to open or gain access to the 1. Tumbling Mixer / Blending (YRDOT)
content or obtain a harmful amount of contents  Y Cone, Rotating Cube, Double Cone, Oblique
 Based on the principle that a young child is unlikely Cone, Twin Shell Or V Mixer
to coordinate two or more separate actions to 2. High Speed Mixer Granulator
achieve a successful opening 3. Fluid Bed Mixer – tablet granulation to dry faster
2. Taper resistant container – uses an indication or barrier to 4. Agitator Mixer – Ribbon and planetary Mixer
entry that is distinctive by design, or must employ an Granules – aggregates of powders that adhere or bond to each
identifying characteristic which if breached or missing can other to form larger unit particles
reasonably be expected to provide visible evidence to  Flowability – Angle of Repose
consumers that tampering has occurred  Compressibility – Hausner’s Ration and Carr’s
 Film wrappers, blister / strip packs, bubble packs, Compressibility Index
shrink seals / bands, foil, paper or plastic pouches,
Methods of Granulation:
bottle seals, tape seals, breakable caps, sealed
1. Wet granulation – aka Wet Massing
tubes, sealed cartons, aerosol containers, can
Types:
Other Container Materials
A. Wet Massing with the use of water (MSD)  30-35% of
Liner Provides additional hermetic
seal water
Inner seal For tamper resistance  Moistening the powders to produce a wet mass
Rubber stopper Hermetic seals for vials  Screening the wet mass to break into granules of
desired size  Sieve
Coil Prevent damage during
shipment  Dry the granules to remove solvent
B. Fluid Bond Granulation Liquid is sprayed on suspended
Desiccant Absorbs moisture
powders
Package insert Others: Metal, rubber, paper
and board Wet Granulators (SSSH)
1. Shear Granulators
Cold Place < 8°C 2. High Speed Mixers / Granulators
3. Spray Dryers  produced finely divided particles for
Freezer -25 to -10°C
suspension formulation
Refrigerator 2-8°C
4. Spheronizers / Pelletizers – makes the powder spherical in
Cool 8-15°C shape (higher flowability)
Room Temperature Temperature prevailing at the
Fluid Bed Granulation – a method of tablet production wherein a
area
granulation solution is sprayed onto the suspended particles which
*Controlled Room 15-35°C
would be then be dried rapidly in the suspending air
Temperature
Warm 30-40°C Granulation – process in which primary powder particles are
made to adhere to form larger, multiparticle entities
Excessive Heat Above 40°C
Spheronization – a multistep process used to make uniformly
spherical particles (for controlled release application)
Types of Powder and Granules
2. Dry Granulation – particles are aggregated using high
Powder – mixture of finely divide drugs and particles
pressure
Granules – combination or aggregate of powder
Types:
Bulk (DODI-TAD) Divided aka Chartula
A. Roll compaction method (RGS)
3
  Powders are rolled into dense sheets Pin method / Reciprocating Die Process
 Sheets are granulated using a mechanical 1. Dipping – pairs of the stainless steel pins are dipped into the
granulator dipping solution to simultaneously form the caps and bodies.
 Sieve granules to obtain the desired size The dipping solution is maintained at a temperature of about
B. Slugging Method (SGS) 50°C in a heated, jacketed dipping pan
 Slugging the powders (formation of a large tablet 2. Spinning – the pins are rotated to distribute the gelatine over
called slug) the pins uniformly and to avoid the formation of a bead at the
 Slugs are granulated using an appropriate capsule ends
equipment 3. Drying – the gelatine is dried by a blast of cool air to form
 Sieve granules to obtain the desired size hard shells. The pins are moved through a series of air drying
Types of Granules: kilns to remove water
4. Stripping – a series of bronze jaws strip the cap and body
1. Good granules – particles that pass through sieve 20 and
portions of the capsules from the pins
retained at sieve 40
5. Trimming and Joining – the strapped cap and body portions
2. Fine granules – particles that pass sieve 40
are trimmed to the required length by stationary knives. After
Qualities of Good Granules trimming to the right length, the cap and body portion are
1. As spherical as possible joined and ejected from the machine
2. Uniform in content 6. Polishing –
3. Normal or bell-shaped distribution of particle sizes  Pan polishing – Acela-cota pan is used to
Properties of Granules for Table Production dust and polished
1. Fluidity / Flowability  Cloth dusting – capsule are rubbed with
2. Compressibility cloth
Improvement of Powder / Granule Flowability  Brushing – capsule are feed under soft
rotating brush
1. Alteration of particle size and size distribution
 Use larger particles Pan polishing – a finishing method for hard gelatine capsule
wherein a polyurethane or cheese cloth material lines the polishing
 Reduce the amount of fines
pan. The liner is used to trap, removed dust, imparting gloss to
2. Alteration of particle shape or texture
capsules.
 The more spherical and smoother the particles, the
more flowable Plate process – warm sheet of gelatine is poured on the mold,
3. Alteration of surface forces drug is poured, upper gelatine layer is added, pressure is
 Reduce / increase electrostatic charges applied to form, fill and seal the capsule
 Reduce moisture content Rotary die – gelatine formed into continuous ribbon by RD
4. Alteration of process conditions machine and are consequently brought together, fill is injected
5. Use f flow activators (GAL) between ribbon, sealed with pressure and heat
 Glidants, lubricants and antiadherents Materials for Capsule Shell Making
Capsules Gelatine Partial hydrolysis of collagen form
Hard Gelatine Capsule animals
Types: Gelatine A and B
 Aka Dry filled Capsule (Contains Silica)
Plasticizer For elasticity and flexibility
 Has 12-16 / 13-15% moisture
Glycerine, sorbitol
 Gelatine shells are manufactured in a separate process
(dripping pegs made of manganese bronze in a melted Colorants FD&C
gelatine mixture) Preservatives 0.15% sulfure dioxide
 Shell composed of: Gelatine, water, sugar, colorants, 0.15% Opacifying agent Titanium dioxide
sulfur dioxide, titanium dioxide (opacifying agent) *for large scale, glidants, lubricants
o Has 2 parts: body and cap / head and surfactants may also be
o Has 8 sizes (5 to 000) employed

Soft Gelatine Capsule

Capsule size Estimated (mL) Easier version
 Has 5-8 / 6-10%
(mL)
 Rendered plastic-like with the addition of plasticizers
000 1.40 1.4
(glycerine or sorbitol)
00 0.95 1.0
 Oblong, oval, tube, pearl, suppository-type
0 0.68 0.7
 Filled with pumpable solutions, suspensions, pasty material
or powders formed and sealed in a single manufacture 1 0.50 0.5
process 2 0.37 0.4
 Plate process and rotary or reciprocating die process 3 0.30 0.3
HGC SGC 4 0.21 0.2
12-16 / 13-15% Moisture 5-8 / 6-10% Moisture Content 5 0.13 0.1
Content  For animal use – 000 and 00
Titanium Dioxide – Opacifying Glycerine / Sorbitol –  Largest for human use – 0
Agent Plasticizer Encapsulation Process
0.15% Sulfur Dioxide - Parabens – Preservative 1. Preparation of formulation
Preservative
2. Filling
Pin Method Plate Process  oldest method
3. Sealing
4. Cleaning and polishing
Punch  method of filling HGC Rotary Die / Recriprocating Die
Process  common

4
Bloom strength – load in grams required to push a standard set oxide and Tannic acid
distance into a prepared gelatine gel (6.66%) solution at 10°C. It Coloring agents For aesthetic purposes and product
measures the capsule’ rigidity identification
Tablets Dyes – water Can be natural or synthetic
Parts of a Tablet Press soluble
1. Hopper – loads the granule, responsible for the storage of Lakes – water  FD&C – Food, Drug and Cosmetics
insoluble  D&C – Drug and Cosmetics
the granules
 External D&C – External use only
2. Feed shoe – directs granules from the hopper to the side,
responsible for the distribution of the granules into the side of Flavouring Oils or dry powders are used in formulations
agents color, odor, and flavour must complement one
the tabletting machine another
3. Punch – compress granules into tablet, used to compact the
Sweetening Natural – Sucrose, Honey, Stevia (SHS)
granules into tablet agents  Sucrose – Saccharum officinale;
 Hardness variation – problem
sugarcan, sugar beet, sugar maple
4. Die – control the size and shape of the tablet  Honey – Apis mellfera
5. Cam tracks – guides the movement of the upper and lower  Stevia – Stevia rebaudiana
punches
Excipients Used in Formulating Tablets Artificial – Cyclamate, Aspartame, Acesulfame
Diluents / Fillers Add necessary bulk to the formulation K, Saccharin, Sucralose (CAASS)
 Cyclamate – 30x as sweet as
Examples: Lactose, Starch, Sorbitol, Kaolin, sucrose (carcinogenic)
Avicel (Microcrystalline Cellulose)  Aspartame – 160 to 200x;
containidcated in patients with
Phenylketonuria
Lactose - common and compatible with  Ascesulfame – 200x; used in
alkaline drugs confectionary
Binders / Promotes adhesion of the particles  Saccharin – 300x; bitter aftertaste
Adhesives  Sucralose – 600x; sweetest
Examples: Starch, Acacia, Algin, Cellulose, synthetic sugar
Gelatine, Liquid Glucose, Povidone, Starch is used as a binder outside the body but when it has
Cornstarch, Tragacanth contact with body fluids it will become a disintegrant
Disintegrant + Lubricant = Running Powder
Starch paste – most common; binder of choice
Colorants
for moisture sensitive materials
1. FD&C Red No. 2 (Amaranth)
Disintegrants Promotes breakup of the tablet after
administration  Causes cancer in rates, unproven safety
2. FD&C Red No. 4 (Maraschino cherries)
Examples: Cellulose (Methocellulose,  Found in maraschino cherries and ingested drugs;
Alginates, SCMC), Starch, Algin, Sodium only used in external drugs and cosmetics
Starch Glycollate 3. FD&C Yellow No. 5 (Tartrazine)
 Causes allergic type reaction in many people
Sodium Starch Glycollate – superdisintegrant 4. D&C Red No. 22 (Eosine)
 Disintegrate the active ingredient 5. FD&C No. 6 (Sunset yellow)
within 3 minutes 6. FD&C Blue No. 2 (Brilliant blue)
Glidants Improve flow properties of granules 7. FD&C Red No. 40 (Allura red)
Flavorants
Examples: Colloidal Silica, Cornstarch, Talc, Cocoa powder Combats bitter tastes of the drugs
Fumed Silicon Oxide, Magnesium Stearate Citrus flavour Combats acid or sour
Raspberry flavour Masked salty taste of the drugs
LMW Salts Salty Flavored Syrup
HMW salts Bitter Eriodictyon Bitter taste
Increase OH group Increased bitterness Glycyrhizza Saline
N-containing Bitter Acacia Urea
Lubricants Reduces friction during ejection of tablets from
the machine to prevent picking
Animal Secretion for Formulation of Fragrance:
Examples: Magnesium Stearate, Calcium Avette Cat
Stearate, Zinc Stearate, Mineral Oil, Carbowax Ambergris Sperm whale
400, Leucine, And Colloidal Silicon Dioxide Musk Deer
Anti-adherents Prevents tablet ingredients from sticking to
punches and dies during the production
Methods of Tablet Manufacture
1. Dry granulation
Example: Magnesium Stearate, Talc
2. Direct compression
Adsorbents Agent capable of holding the molecule onto
their surfaces 3. Fluid bed processing
4. Wet granulation
Examples: Activated Charcoal Tablet Coating
A. Sugar-coating (PPP)
Activated Charcoal – component of the  Successive addition of sucrose-based solutions to
universal antidote together with Magnesium a tablet core

5
3 Processes 1. Spansule – a capsule composed of hard gelatine shell
1. Pan coating – most widely used containing hundreds of tiny coated beads / pellets of drugs for
2. Pan spraying sustained release. Ends of both bodies and cap are highly
3. Pan suspension tapered / narrowed. Used by Smith Kline Beecham.
2. Pulvules – end of the body-producing peg is tapered but the
Steps in Sugar-coating (SSSFP)
cap-making peg is rounded. Used by Eli Lilly.
1. Sealing / waterproofing – for components easily affected by
3. Kapseal – this is a distinctive looking capsule because of the
water; example: Shellac
sealing with a colored ban of gelatine. This is used by Parke-
2. Subcoating – improve bond between sugar coat and tablet
Davis
core; round off contours and to achieve desirable size;
4. Coni-Snap – the rim of the capsule body is not straight but
examples: Acacia and Gelatine solution
tapered slightly. This eliminates splitting of the joined
3. Syruping / smoothing - complete rounding off
capsule.
a. Glossing – establishing color base
A pH-sensitive, non-digestible radiofelemettric device, used as a
b. Heavy syruping – build a solid color base rapidly
nonradioactive means of measuring gastric pH, gastric residence
c. Regular syruping – to attain appropriate color
time and gastric emptying time of solid dosage forms is called
4. Finishing – to attain final smoothness
HEIDELBERG CAPSULE.
a. Debossed – imprinted with a mark below the
surface Tablet Processing Problems
b. Embossed – imprinted with a mark above the  Separation – Capping, Chipping, Lamination
surface  Removal – Picking, Flaking
5. Polishing – for sheen or gloss; examples: Beeswax and  Adhesion – Sticking, Blistering, Wrinkling
Carnauba wax  Migration – Spotting, Blooming, Mottling
 Tablet Press Problem – Weight Variation, Hardness
B. Film-coating (FAPSOSGV) Variation
 The process of placing a thin, skin-tight coating of a  Others – Orange peel, Bridging, Sweating, Tablet
plastic-like material over a tablet core erosion, Filming, Cratering, Blushing, Cracking, Rocker
 Advantage: No significant increase in tablet size bottom
and weight unlike sugar-coating (50% increase of
the thickness of the tablet) 1. Capping – separation of top and bottom
 About 2-5% increase in thickness only 2. Chipping – separation of small portion (friability)
Excipients Used for Film-coating: 3. Lamination – separation of several layers
1. Film former – produces smooth thin film 4. Picking – removal of top layer (punch)
 Examples: Cellulose acetate phthalate, 5. Flaking – removal of small portion of liquid
Hydroxypropylmethylcellulose (HPMC) 6. Sticking – adhesion of the material to the die wall
2. Alloying substance – provide water solubility / permeability 7. Blistering – reduce adhesion of film from the tablet due to
to the film to ensure penetration by body fluids improper drying
 Examples: Polyethylene Glycol (PEG) 8. Wrinkling – reduce adhesion with many blister
3. Plasticizer – produces flexibility and elasticity during 9. Orange-peel – roughness of tablet surface
application 10. Bridging – filling in of the score line
11. Sweating – formation of oil film droplets of liquid
 Examples: Castor oil, PG, Glycerin, PEG
12. Blooming – dull migration of plasticizer
4. Surfactant – enhance spreadability of the film during
13. Spotting – migration of the other ingredient
application
14. Mottling – migration of color
 Examples: Spans (W/O) and Tweens (O/W)
15. Weight variation – problem with die
i. Non-ionic surfactant – spans and
16. Hardness variation – problem with punches
tweens
17. Tablet erosion – disintegration of the core tablet
ii. Cationic – quaternary ammonium
18. Filming – slow form of sticking
compound
19. Cratering – defect of film coating whereby volcanic craters
iii. Anionic – sodium lauryl sulfate
appear
5. Opaquant and Colorant – to enhance aesthetic qualities of
20. Blushing – whitish specks / haziness in the film
the coat
21. Cracking – due to rapid expansion of tablet
 TiO2, FD&C
22. Rocker bottom – sunken center formation
6. Sweetener, flavour and aroma – enhance acceptability of
the tablet by the patient Solutions – homogenous one phase system consisting of 2 or
 Examples: Vanillin, Saccharin more components. Most commonly used liquid dosage form. pH:
7. Glossant – produces luster to the tablet 4.8 or greater
 Examples: Beeswax 1. Active ingredient – consider solubility and stability
8. Volatile solvent – allows the spread of other compound over 2. Solvent – consider clarity, toxicity, viscosity, compatibility,
the tablet while allowing rapid evaporation to permit an palatability
effective yet speedy operation  Water – best solvent
 Examples: Alcohol-acetone mixture 3. Co-solvent – used in combination with the solvent to
increase solubility of the solute; semi-polar solvent
C. Enteric coating  Ethanol, Sorbitol, Glycerine, Propylene Glycol,
 Designed to resist dissolution in the stomach but Polyethylene Glycol
dissolve in the less acidic environment of the small 4. Solubilizer – surfactants (reduce surface tension)
intestines  Tweens
 pH: 4.8 or greater 5. Viscosity enhancer / controller – improves pourability and
 Examples: Shellac, CAP, PAP to some extent, palatability
 Sugar, PVP, Cellulose derivatives
Specialized Type of Capsules
6. Buffer – controlling pH to maintain solubility and stability

6
  Most common; pH 4-7 General Formulation of Emulsion
 Citric, Lactic, Glutaric 1. Active ingredient
7. Sweetening agent 2. Aqueous phase (water soluble)
8. Flavour 3. Oleaginous phase (water insoluble)
9. Coloring agent 4. Emulsifier – acts as the bridge between the 2 immiscible
10. Preservative – benzoic acid and its salts, parabens, phases, stabilizer of the internal phase, retards coalescence
chlorobutanol, benzyl alcohol, thimerosal,m benzalkonium of the globules
chloride 5. Antioxidants – protects the emulsified lipids which are
General Steps in the Manufacture of Pharmaceutical susceptible to oxidation. Examples: BHA, BHT, Tocopherol,
Solutions Ascorbic acid, EDTA
1. Preparation of formulation materials and equipment 6. Preservative – should be effective for both phases
2. Compounding – 7. Sweetener
 Charge the solute to the solvent 8. Flavouring agent
9. Colorant
 Agitate with the use of mixers until solution is
10. Humectants – reduces the evaporation of moisture from the
homogenous
product; prevents drying. Examples: Glycerin, Sorbitol,
 Heat may be employed to increase solubility
Propylene glycol
 Ensure complete solution before further processing
 Solutes in small concentrations (such as dyes and Manufacturing Process
intensely colored materials) must be predissolved 1. Oil phase containing oil-soluble ingredients is heated at
prior to mixing with the whole batch about 5-10°C above the melting point of the ingredient with
3. Storage and aging – to allow complete blending of all the the highest melting point
components 2. Aqueous phase is heated to the same temperature
4. Filtration and Clarification (GVPPS) 3. The two phases are mixed
 Aim for 3-5 microns or less 4. Volatile ingredients are added at the lowest temperature as
i. Filter media: cellulose nitrate, polyamide, possible (usually 45-55°C)
polyvinylidene chloride, nylon 5. Adjust the final weight when emulsion reaches 35°C
 Classified as: Equipment
i. Gravity filtration – slow 1. Mechanical stirrers
ii. Vacuum filtration – large scale 2. Colloid mills – homogenization of viscous emulsions
iii. Pressure filtration – fast, to achieve  An equipment that mixes the components of
highly polished product emulsion by means of various impellers on shafts,
iv. Parallel filtration – one type of filter which are placed directly into the system to be
v. Series filtration – more than one filter emulsified
5. Filling and Packaging (GVP) 3. Homogenizers –
 Gravimetric filling – for mobile and frothy  This equipment produces finely divided particles by
solutions spraying a mist of liquid through a heated chamber,
 Vacuum filling – for viscous solutions drying immediately and collecting the dried
 Pressure filling – for viscous solutions powders in a clean receptacle
General Scheme for Suspension HLB Value Range Surfactant application
1. Active ingredient – should be insoluble, must be uniformly 0-3 Antifoaming agents
dispersed 4-6 W/O emulsifying agents
2. Dispersion medium – aqueous or non-aqueous; solvent 7-9 Wetting agents
3. Wetting agent – displaces the air from crevices of drug 8-18 O/W emulsifying agents
particles
13-15 Detergents
 Glycerine, Sorbitol Solution, Syrup
10-18 Solubilising agents
4. Suspending agent – increase the viscosity of suspension,
avoid fast settling of particles  Hydrophilic substance
 Hydrocolloids – Acacia, Tragacanth, Veegum,  Lipophilic substance
Cellulose Derivatives  HLB number usually between 1 and 20 are used as
 Clays – Bentonite, Kaolin emulsifying agents
 Others – Agar, Gelatine, Pectin, Gelatinized Starch  With values 8 to 18 indicates hydrophilic molecule
(produce o/w type of emulsion)
 Bentonite – 10% dispersion in water
 Lower numbers in the range of 3 to 6 indicates lipophilic
 Acacia – 35%
molecules and will produce w/o emulsions
 Tragacanth – 6%
5. Buffer Aerosols – pressurized dosage forms designed to deliver drug
6. Sweetening agent systematically or topically with the aid of liquefied or propelled gas
7. Flavouring agent  Product concentrate – active ingredient combine with
8. Colorant excipients
9. Preservative  Propellant – act as a solvent and diluents; carrier
Emulsion – are dispersed systems in which the dispersed phase Pressure of the propellant forces the liquid phase up the tube and
is composed of small globules of a liquid distributed throughout a out in the atmosphere  propellants meet the air  evaporates
vehicle in which it is immiscible due to drop in pressure  leaving the product concentrate as
Types of Emulsion airborne liquid droplets or dry particles, as in powders
1. Oil in water Propellant
2. Water in oil Liquefiable gas Chlorofluorocarbon (CFC) – can degrade
3. Multiple emulsion the ozone layer
4. Microemulsion

7
 Dicholorodifluoromethane, B. Compounding Area
Dichlorotetrafluoroethanes,  Most stringent control
Trichloromonofluoromethane –  Stainless steel cabinets and counters
alternatives
 Continuous surfaces
Compressed gas Include carbon dioxide, nitrogen, nitrous
 Class 100 environment (nmt 100 little particles)
oxide
C. Aseptic Filling Area
 “heart” of the production area
Parts of Aerosol
 Laminar air flow (LAF) with HEPA filter (High
1. Actuator – provides a rapid and convenient means for Efficiency Particulate Air)
releasing the contents from a pressurized container; button  Laminar air flow hood
that activates the system i. Vertical – responsible for protecting the
2. Valve – expels the contents from the container; regulate the person or environment
flow of product from container ii. Horizontal – responsible for protecting
3. Stem – part of the usual aerosol valve assembly that the product
supports the actuator and delivers the formulation in the  99.95% efficiency
proper form  Used to test efficiency of HEPA filter –
4. Dip tube – the tube that delivers the content Dioctylphthalate Test (DOP TEST)
5. Gasket – placed snugly with the stem, prevents leakage of D. Quarantine Area
the formulation when the valve is closed
 Storage while waiting for QC results
6. Mounting cup – part of the usual aerosol valve assembly
E. Finishing Area
that is attached to the aerosol can or container and hold the
Active Ingredient and Excipients in Parenteral Preparation
valve in place
7. Spring – holds the gasket in place and is the mechanism by 1. Active drug
which the actuator retracts when pressure is released, 2. Solvent / Vehicle
returning the valve to the closed position  Aqueous – Ethanol
 Water miscible – Propylene Glycol
 Water for injection – PEG 450 and 600
 Glycerine
 Vegetable oils – Sesame, Peanut, Corn,
Cottonseed oil
 Solvents for IM injections
 Non-vegetable oils - Benzyl Benzoate, Ethyl
Oleate, Isopropyl Myristate
3. Other excipients – Buffer, Acetates, Citrate, Phosphates
4. Preservative – Chlorobutanol, Benzyl Alchol, Parabens
5. Chelating agent – EDTA
6. Tonicity Adjusting Agent – NaCl, Boric acid, NaNO3,
KNO3, Dextrose
7. Containers – bottle, vial, ampule, cartridge, bag, glass,
plastic
 Single-dose: limit 1000ml
 Multiple-dose: limit 30mL
8. Closures / Stoppers
Manufacture of Sterile Products
Should be carried out in clean areas, entry to which should be
through airlocks for personnel and/or for equipment and materials
Clean areas
An area with defined environmental control of particulate and
Different Types of Sterile Preparations microbial contamination constructed and used in such a way as to
1. Biologicals – vaccine, toxoid, antisera reduce the introduction, generation, and retention of contaminants
2. Sterile products – sterile solution, sterile suspension within the area
3. Parenterals – administered intravenously, IM Airlock
4. Ophthalmics – administered through the eyes
An enclosed space with two or more doors, which is interposed
Category of Sterile Preparation (LEDDSS) between two or more rooms
 Solutions ready for injection Different Clean Areas of a Manufacturing Company
 Dry soluble products ready to be combined with a solvent
 Grade A
prior to uses
o Local zone for high risk operations
 Suspensions ready for injection
o Examples: Filling zone, stopper bowls, open
 Dry insoluble products ready to be combined with a vehicle ampoules and vials, aseptic connections
prior to use o Provided by a laminar air flow work station with a
 Emulsions ready for injection HEPA
 Liquid concentrates ready for dilution prior to use  Grade B
Production Facilities for Parenteral Preparation o For aseptic preparation and filling
 Easy to clean, safe and sterile  Grade C and D
A. Materials Support Area o Clean areas for carrying out less critical stages of
 Surfaces should be continuous the manufacture of sterile
 Class 10,000 environment (nmt 10,000 particles or  Class C
0.5um or larger are present in per cubic ft.) o Hair and where relevant beard should be covered
8
 o A single or two piece suit gathered at the wrist and requirements for the absences of pyrogens,
with high neck and appropriate shoes or overshoes otherwise use additional 5 rabbits
should be worn should shed virtually no fibers or o If not more than three of the eight rabbits show
particulate matter individual rises in temperature of 0.5°C or more
 Grade D and if the sum of the eight individual maximum
o Hair and where relevant beard should be covered temperature rises does not exceed 3.3°C, the
o General protective suit and appropriate shoes and material under examination meets the
overshoes should be worn requirements for the absence of pyrogens.
o Appropriate measures should be taken to avoid Fine dispersion 1-10 microns
any contamination coming from outside and clean True solution <1 microns
areas
Colloidal dispersion 1-0.5 microns
Sterilization Coarse dispersion >0.5 microns
1. Steam (Protein Denaturation) Suspension >0.5 microns
 Autoclave – 121°C, 15-30 minutes, 15psi Parenteral and inhalational 1-5 microns
2. Dry heat (Oxidation) suspension
 Oven – 160-170°C, 2-4 hours, 650°C in 1 minute, Impalpable powder 74 microns
250VC in 45 minutes, and 180VC in 4 hours Micronization <5 microns
3. Tyndallisation (DNA Mutation)
Fluid or jet milling <10 microns
 Intermittent steam sterilization exposing material to
Cold sterilization 0.2 microns
100°C for 30 minutes or at 80°C for 1 hour for 3
Oral aerosols Below 50 microns
consecutive days
4. Gas – Ethylene oxide (Denaturation) Micropulverization 10-50 microns
5. Ionizing Radiation UV (DNA Unwinding) Spheronization 0.512 microns
 240-280nm; bactericidal (gamma, cathode, beta
rays) 70-72°C Avoid breaking in semisolid
6. Bacterial Filtration–membrane filters (Mechanical 2-8°C Storage of biological
Separation) – separates the bacteria 40-45°C Temperature thermally bond capsule’s cap and
Biological Indicators for Sterilization – test the efficiency of body
sterilization process -34.5 - - Propellant in aerosol liquefies
1. Steam – B. stearothermophilus 40°C
2. Dry heat – B. subtilis 65°C for 1 Destroyed pyrogen contaminating glasswares
3. Ionizing radiation UV – B. pumilus, B. stearothermophilus, minute
B. subtilis 250°C for Destroyed pyrogen contaminating glasswares
4. Ethylene oxide – B. subtilis 45
minutes
5. Membrane filtration – P. diminuta
180°C for Destroyed pyrogen contaminating glasswares
Quality Control 4 hours
 Environment: >49°C Aerosol container burst
 Blood agar plate 100°F Empty HGC should be stored
 RODAC contact plates
o Replicate Organism Detection and Counting –
count the microbial particles in a certain
environment
 Product: Sterility test, Pyrogen Test
Packaging and Labeling
Methods to seal ampoules
1. Tip Seal Method or Bead Seal – not so efficient, long
method
2. Pull Seal – more efficient
Leakers Test – test the integrity of strips, blisters and bottles.
Operation based on vacuum. It uses 1% Methylene Blue
Pyrogen Test:
 Bacterial Endotoxin Test – This is a test for estimating
theconcentration of bacterial endotoxins
o Endotoxins react with enzyme Limulus Amebocyte
Lysate (LAL) forming gel clot formation or turbid
solution
o LAL are obtained from aqueous extracts of the
circulating amebocytes of the horseshoe crab,
Limulus polyphemus
 Quantitative Fever Response Test – uses rabbit
o Involves measuring the rise in temperature of the
rabbits following the intravenous injection of a test
solution and measuring the temperature for 1-3
hours at 30 min interval
o If no rabbit shows an individual rise in temperature
of 0.5°C or more above, the product meets the

9
 4 o'clock habit -
cleaning the
environment

Biostatistics - branch of medicine that deals

with the incidence of distribution as well as the
possible control of the disease and other
factors in relation to health. (fall under
epidemiology )

abx resistance -->

 portion of
antigen

-First line of defense for infections

most abundant

Lymphocytes: B cell
T cell
Natural killer cells

cell eating

Erythropoeitin- hormone release by the kidneys

Kidney- initiates the release of RBC
Convave is the normal shape of RBC; transformed to other shape=sickle cell anemia(irregular shape-no ability to carry oxygen)
B lymphocyte= Build
T-lymphocyte= Transfer Immunity- artificially
Platelets- responsible for clotting including immunity or
provide protection from
disease

Innate Immunity- "Born

Ready"
- acts immediately on
pathogen (non-specific)
- Don't require activation

Examples:
Physical Barriers( Skin,
Mucous membrane)

Chemical Barriers
( Lysozyme, Sweat,
Stomach acid)

Inflammatory Response
(Mast cells---> Histamine)

Adaptive Immunity- "

Learn and remember"
- respond on specific
pathogen
-requires activation
-forms a memory cell to
protect us from future
attack. Phagozome-
surrounds the
Example; T helper cell pathogen inside
will be activated by a the cell wherein
certain antigen. T helper iineengulfs sya don
cell will activate cytotoxic
cell and b cell. Cytotoxic
cell will attack the
pathogen directly. B cell
will make antibodies
(plasma cell)
Cytotoxic will create
memory T cell while B
cell will create memory B
cell.
 T cells - matured in thymus
gland
- " thymocyte"

Cd4 T cell- attacks by HIV

B cells- produce in bone

marrow

Primary response
Log/ Exponential Phase - IgM appears first
- rapid increase in conc. IgG
Antibody conc of antibodies against Plateau/ Stationary/ Steady phase
- proliferating B cells start to
switch to IgG producing cells
pathogen - antibody synthesis is equal to -slow Secondary response
antibody deterioration -short - IgM is produced in small quantity, short period of time
- long lag phase - IgG is produced in large quantity
then later mapoproduce na din sila IgA, IgE
Lag/Latent Decline Phase
- rapid
- No detectable antibodies - antibody conc. starts to decline
-strong
time -short lag pahse

1.Passive Immunity
- Immediate response
- short term protection
- host receive the antibody
from other source.

Natural Passive
-host will receive antibody
from other organism
Ex: IgG from placenta
Breastmilk

Artificial Passive
-received manufactured
antibody
Ex: Blood transfusion of
monoclonal antibody
Y shape
2.Active immunity Ganid, gahaman= responsible in secondary response and can cross the placenta
- long term protection
- host create their own
antibody( exposure) Malaki,
- Lymphocytes form memory
cells

Natural Active
- produce antibody in Alat= body secretions
response to exposure a
pathogenic infection
epal: E- parasitic allergic rxn
Artificial active
-exposure to attenuated
(weak) unknown
pathogen--->Vaccination
 allergic reaction that is provoke by the reexposure to specific type of -small doses
antigen= Allergen
Ex: Anaphylactic reaction

-multiple dose

-antibodies are produced by the immune response that will later on

bind to antigen own surface
ex: Acute rheumatic fever, autoimmune diseases
OUR LADY OF FATIMA UNIVERSITY
College of Pharmacy
PHARMACEUTICAL SEMINAR 2

PHARMACEUTICAL
COSMETICS
(PART 1)
 UNIT OUTCOMES

At the end of this unit, the students are

expected to:
◉Demonstrate familiarity on cosmetic science
terminologies.
◉Demonstrate knowledge on the principles
and methods involved in formulation of
cosmetic products the science of cosmetics
◉Describing the GMP requirements for
cosmetics.
◉Identify the requirements for cosmetic
notification.

2
 checklist

◉ Read unit outcomes and unit objectives

◉ Read course guide prior to class
attendance
◉ Proactively participate in discussions
◉ Watch videos related to the topic
◉ Participate in discussion board (Canvas)
◉ Answer and submit course unit tasks

3
Required Readings

◉ Baki, G., & Alexander, K. S. (2015).

Introduction to Cosmetic
Formulation and Technology. New
Jersey, USA: John Wiley & Sons.
◉ Iwata, H., & Shimada, K. (2013).
Formulas, Ingredients and
production of Cosmetics. Tokyo,
Japan: Springer Japan.
◉ Tadros, T. F. (2016). Formulations: In
Cosmetic and Personal Care. Berlin:
de Gruyter Publisher.

4
 !"#$"%#&'!('
)!*+#,%)'*)%#-)#
“

5
COSMETIC
SCIENCE
• What is Cosmetics?
• Cosmetics means any article intended to be
rubbed, poured, sprinkled or sprayed on, or
introduced into, or otherwise applied to, the
human body or any part thereof for cleansing,
beautifying, promoting attractiveness, or
altering the appearance, includes any article
intended for use as a component of cosmetic.

6
HISTORY
• The word ‘‘cosmetic’’ is derived from the
Greek word Kosm tikos, meaning ‘‘having the
power to arrange, skilled in decorating giving
kosmein, ‘‘to adorn,’’ and kosmos, ‘‘order,
harmony’’,
• But the true origin of cosmetics probably lies
further still in antiquity, because early cave
paintings of 30,000 years ago depict the use of
body adornment (rudimentary cosmetics) in
the rituals of mating and hunting.

7
 Several historical vignettes showing the role of
cosmetics down through the ages:
• Vases of alabaster and obsidian for cosmetics discovered
by Flinders Petrie in 1914 illustrate that the ancient
Egyptians were well versed in the use of eye and face
paints, body oils, and ointments.
• Theophrastus (363–278 BC), a student of Aristotle,

HISTORY demonstrated considerable knowledge of the

compounding of perfumes,
• The Roman physician, Galen of Pergamon (130–200 AD),
is said to have innovated that timehonored toiletry: cold
cream (Cera Alba).
• The Babylonians were said by Herodotus (490–420 b.c.) to
be well practiced in the use of depilatories and the eye
adornment.
• Alexander the Great (356–323 b.c.) reported the use of
unguents, incense, and other cosmetics by the countries of
the Indo-Sumerian civilization.

8
TYPES OF COSMETICS
INGREDIENTS

• Functional ingredients are the ones that provide the benefit

of cosmetics. They include cleansers (surfactants), conditioning
agents, colorants, fragrances, reactive ingredients, film formers,
and drug actives. Every cosmetic you’ve ever used or made has
at least one functional ingredient.

• Aesthetic ingredients are those that help make delivery of

the functional ingredients more acceptable. These are ingredients
like solvents, thickeners, preservatives, fragrances, pH adjusters,
plasticizers, fillers, appearance modifiers, anti-oxidants, anti-
irritants, and delivery systems.

• Claims ingredients are ingredients added to a formula at a

low level for the primary purpose of getting to put the ingredient
name on the label. This includes ingredients like natural extracts,
vitamins, proteins, biotechnology, and fanciful made-up ingredient
names.

9
ASEAN GUIDELINES FOR COSMETIC GOOD
MANUFACTURING PRACTICE

10
ASEAN GUIDELINES FOR
COSMETIC GOOD
MANUFACTURING PRACTICE
• Quality Management System
• A quality system should be developed,
established and implemented as a means by
which stated policies and objectives will be
achieved. It should define the organisational
structure, functions, responsibilities,
procedures, instructions, processes and
resources for implementing the quality
management.

11
ASEAN GUIDELINES FOR
COSMETIC GOOD
MANUFACTURING PRACTICE
• Personnel
• There should be an adequate number of
personnel having knowledge, experience, skill
and capabilities relevant to their assigned
function. They should be in good health and
capable of handling the duties assigned to
them.

12
ASEAN GUIDELINES FOR COSMETIC GOOD
MANUFACTURING PRACTICE

• Premises
• The premises for
manufacturing should be
suitably located, designed,
constructed and maintained.
 ASEAN GUIDELINES • Equipment
FOR COSMETIC GOOD • Equipment should be designed and located to
suit the production of the product.
MANUFACTURING • Design and Construction
PRACTICE • Installation and Location
• Maintenance

14
ASEAN GUIDELINES FOR COSMETIC
GOOD MANUFACTURING PRACTICE

• Sanitation and Hygiene

• Sanitation and hygiene
should be practiced to avoid
contamination of the
manufacturing of products. It
should cover personnel,
premises,
equipment/apparatus and
production materials and
containers.
15
16

ASEAN GUIDELINES FOR

COSMETIC GOOD
MANUFACTURING PRACTICE
• Production
• Starting Materials
• Batch Numbering System
• Weighing and Measurement
• Procedure and Processing
• Dry Products
• Wet Products
• Labelling and Packaging
17

• Starting Materials
• Water - Special Attention should be paid to
water, since it is an important raw material.
Water production equipment and water
systems should supply quality water. Water
systems should be sanitized according to
wellestablished procedures.
PRODUCTION • Verification of materials - All deliveries of raw
materials and packaging materials should be
checked and verified for their conformity to
specifications and be traceable to the product.
• Rejected materials - Deliveries of raw
materials that do not comply with specification
should be segregated and disposed according
to standard operating procedures.
PRODUCTION
• Batch Numbering System
• Every finished product should bear a
production identification number which
enables the history of the product to be
traced.
• A batch numbering system should be
specific for the product and a particular
batch number shall not be repeated for the
same product in order to avoid confusion.

18
PRODUCTION
• Dry Products
• Handling of dry materials and products
should be given special attention. Where
possible, dust-containing production
system, central vacuum system or other
suitable methods should be employed.
• Wet Products
• The used of closed systems of production
and transfer is recommended.

19
PRODUCTION
• Labelling and Packaging
• Packaging line should be inspected for
clearance prior to operation. Equipment
should be clean and functional. All materials
and products from previous packaging
operation should have been removed.
• Samples should be taken and checked at
random during labelling and packaging
operations.
• Each labelling and packaging line should be
clearly identified to avoid mixup.

20
ASEAN GUIDELINES FOR
COSMETIC GOOD
MANUFACTURING
PRACTICE
• Quality Control
• Quality control is an essential part of
GMP. It provides assurance that
cosmetic products will be of consistent
quality appropriate to their intended
use.
• Reprocessing
• Returned Products
 • Internal Audits
• An internal audit may be
conducted by outside or
independent specialists or
a team designated by the
management for this
purpose. Such audits may
also be extended to
suppliers and contractors,
if necessary.
ASEAN GUIDELINES FOR
COSMETIC GOOD
MANUFACTURING PRACTICE
22
 • Storage
• Storage areas should
be of sufficient
capacity
• Storage areas should
be designed or
adapted to ensure
good storage
conditions.

ASEAN GUIDELINES FOR

COSMETIC GOOD
MANUFACTURING PRACTICE
23
REGULATORY ISSUANCE GOVERNING COSMETIC
PRODUCT NOTIFICATION

24
REGULATORY ISSUANCE GOVERNING
COSMETIC PRODUCT NOTIFICATION

• The company or person responsible for placing the

cosmetic products in the market must notify the
regulatory authority responsible for cosmetics of each
Member State where the product will be marketed, of
the place of manufacture or of initial importation before
the product is placed in the market, using the Product
Notification Form prescribed by the regulatory authority.
• The product can only be marketed after notification has
been sent to the regulatory authority and
acknowledgement has been received.
REGULATORY ISSUANCE GOVERNING
COSMETIC PRODUCT NOTIFICATION
• Aiming to streamline the process
by updating the submission of
application requirements from the
previously manual form to online
submissions, the Food and Drug
Administration (FDA) allowed online
application process.
• This modernization was kickstarted
in March 2013 through FDA
Memorandum Circular No. 2013-
011.
REGULATORY ISSUANCE GOVERNING
COSMETIC PRODUCT NOTIFICATION
• What Information should be Declared in the
Product Notification?
• Brand Name/Product Name/Product Variants
• Product Type
• Particulars of the Product
• Intended Use
• Product Presentations
• Local Company Responsible for Placing the
Cosmetic Product in the Market
• Establishment Information
• Person Representing the Local Company
• Product Ingredient List
REGULATORY ISSUANCE GOVERNING
COSMETIC PRODUCT NOTIFICATION
• Procedures in the Application for
Cosmetic Product Notification in the
Philippines

• The application process has four (4)

main parts:
• Submission
• Payment
• Download Result, and
• Revalidation
APPLICATION
PROCESS
• 1.Submission:
• - This is now done through the FDA’s
portal at https://www.fda.gov.ph
• - Once you have filled up the
necessary details of the cosmetic
product to be notified, you can
submit the application with the FDA
through their portal.
• 2.Payment:
• - Filing fee depends on the number
of years of the validity of the
registration.
APPLICATION
PROCESS
• 3.Download Results
• - There are instances when the FDA will
send an email requiring additional
documents or information concerning the
application.
• - Compliance with the email by submitting
the required documents or supplying the
needed information is a requisite to the
FDAs approval of the notification.
• - On the other hand, the failure to comply
with the additional documents or information
required will lead to the rejection of the
application for notification.
APPLICATION
PROCESS
• 4.Revalidation
• - Acknowledged cosmetic
notifications may be revalidated
for a new validity date, where the
new validity date will be based on
the date of submission of the
revalidation application.

31
Hair Products
“

32
HAIR
PRODUCTS
• Hair and Hair Follicles
• Hair is composed primarily of proteins
(88%) These proteins are of a hard fibrous
type known as keratin. Keratin protein is
comprised of what we call "polypeptide
chains.”
HAIR PRODUCTS

• Chemical Composition of
Hair
• • Hair made up of 20 amino
acids.
• - Body produces 11 of
the 20, the remainder must
come from diet.
• • Proteins are sources of
amino acids.
• • A healthy diet is necessary
for healthy hair.
HAIR PRODUCTS

• Hair Color
• • All natural hair colors are the
result of two types of hair
pigments.
• • Both of these pigments are
Melanin types, produced inside
the hair follicle and packed into
granules found in the fibers.
• • Eumelanin is the dominant
pigment in brown hair, and black
hair while pheomelanin is
dominant in red hair.

35
TYPES OF HAIR
• • Vellus (lanugo) hair:
short, fine, downy,
unpigmented hair on
body.
• • Terminal hair: long,
thick, pigmented hair
found on scalp, legs,
arms, and body.

36
SHAPES OF
HAIR
• The shape of the hair
shaft determines whether
hair is straight or curly.
• • If the shaft is round, the
hair is straight.
• • If the shaft is oval, the
hair is wavy.
• • If the shaft is flat, the
hair is curly or kinky.

37
38
ANATOMY
OF HAIR

• I-THE SHAFT
• A- The medulla
• B- The cortex
• C- The cuticle

• II-THE ROOT
• A-The hair bulb
• B-The erector pili muscles

39
 HAIR SHAFT

There are 3 main layers of the hair

shaft.
1. CUTICLE: The outermost layer of
the hair.
2. CORTEX: The middle layer of
hair; a fibrous protein core
formed by elongated cells
containing melanin pigment.
3. MEDULLA: Innermost layer; also
referred to as the pith(Core) of
the hair.
40
 HAIR LIFE CYCLE

Active-Growth Phase (ANAGEN): Active growth period is 2-

5 years before replacement.

Transition Phase (CATAGEN): lasts one or two weeks &

hair follicle shrinks about 80%.

Resting Phase (TELOGEN): After five or six weeks, dermal

papilla reconnects to base of hair follicle and bloodstream.
The hair re-enters the active-growth phase and a new hair
begins to from.

41
SHAMPOO
• The word shampoo is
derived from Hindustani
chāmpo.
• Shampoo is a hair care
product that is used for
the removal of oils, dirt,
skin particles, dandruff,
environmental pollutants
and other contaminant
particles that gradually
build up in hair.

42
CLASSIFICATION OF SHAMPOO

• I. Based on Appearance
• a) Powder Shampoos
• b) Liquid Shampoos or Lotion
• c) Gel Shampoos or Solid Cream
• d) Cream Shampoos
• e) Oil Shampoos
• f) Miscellaneous-anti dandruff,
medicated shampoo
 • II. Based on Use
• a) Conditioning
Shampoos
• b) Antidandruff and
Therapeutic
• c) Baby
• d) Balancing
• e) Clarifying

CLASSIFICATION
OF SHAMPOO
44
COMPOSITIONS OF
SHAMPOO
• a) Water
• b) Surfactants
• c) Foam boosters and stabilizers
• d) Opacifiers
• e) Clarifying agents
• f) Antidandruff agents
• g) Conditioning Agents
• h) Thickening agents
• i) Sequestering Agents

45
HAIR TONICS AND
CONDITIONERS
• The term “hair tonic” has been used for some
hair preparations because the term is used in
therapeutics. Hair tonic is one kind of hair
repairing tonic and re-texturing the hair. There
are two distinct types of products :
• 1.Products those deals with specific
problems of the hair. E.g., greasy hair,
dandruff.
• 2.Those products which are intended for
improving, restoring, & maintaining the
condition of the hair.

46
 47

HAIR TONICS AND

CONDITIONERS
• Medicated Products
• The purpose of this products is to cure, to
reduce, to restrain & some abnormality in
the function of scalp.
• In the past, use was often made of irritant,
keratolytic, rubifacient compounds.
• The recent trend is that the treatment
should rather bring about a return to a
normal state & promote balance.
• Medicated products are mainly deal with
dandruff, seborrhea & hair loss.
HAIR TONICS AND
CONDITIONERS
• Conditioners
• Hair conditioners are viscous liquid that is applied to
the hair & are usually used after washing the hair with
shampoo.
• It is designed to restore hair to its natural state.
• It has the ability to repair damage hair by
providing shiny look to the hair fibers.
• Hair conditioner restores the texture &
appearance of the rough & harsh hair.
• Hair conditioner are used to render the hair shiny,
easy to comb & free from dryness.

48
TYPES OF
CONDITIONERS
• 1. Pack Conditioners
• - It is heavy and thick.
• - A high content of surfactant it is able to bind
the hair structure & glue the hair surface scale
together & tend to form thicker layer on the
hair surface.
• - These are usually applied to the hair for a
longer time.

49
50

TYPES OF
CONDITIONERS
• 2.Leave in Conditioners
• - They are thinner & have different
surfactants.
• - It is lighter, less viscous mixture & provides
a significantly thinner layer on the hair.
• - This is designed to be used in a similar way
to hair oil preventing tangling of hair & keeping
it smooth.
TYPES OF
CONDITIONERS
• 3.Ordinary Conditioners
• - It combines some aspects of both packs &
leave in ones.
• - These are generally applied after the use of
shampoo.
• - Further, it can be characterized into 3 main
type :
• a)Moisturizer
• b)Re-constructers
• c)Detangles

51
52

ORDINARY HAIR
CONDITIONER
• a) Moisturizers
• - These are organic solvent
concentrated with humectant.
• - Humectant is to retain the moisture
into the hair.
• - This conditioners may not contain
protein.
ORDINARY HAIR
CONDITIONER
• b) Re-constructers
• - It contains proteins for hydrolization.
• - Human hair keratin protein has a low
molecular weight.
• - This protein penetrates the hair shaft &
gives a shiny hair.
54

ORDINARY HAIR
CONDITIONER
• c) Detanglers
• - These are acidifiers & have low pH.
• - The function is to close the cuticle of the
hair, which cause tangles.
• - The protection or shield mechanism is done
by surfactant & polymers.
 • a) Surfactants
• b) Partially or totally
hydrolyzed proteins
• c) Oily materials
• d) Glossers
• e) Humectant
• f) Thickeners
• g) Bodying agent
• h) Perfumes

COMPOSITIONS OF
CONDITIONERS
55
HAIR COLORANTS
• The colouring of hair is one of the most
important acts of adornment among those
made by men and women since the origin of
man. The reasons for getting the hair coloured
have been:
• To change the natural colour
• To colour the white hair which begin to
appear with age
• To change the colour of the hair
temporarily on a particular occasion.

56
 HAIR COLORANTS
• CHARACTERISTICS OF AN IDEAL HAIR COLOURANT
• 1.It should be non-injurious to hair shaft but should colour the hair without impairing the
natural texture and gloss.
• 2.It should possess no primary irritant action and be free from sensitizing properties.
• 3.It should produce no toxic effect when in contact with the skin.
• 4.The colour of the dyed hair should be stable to air, sunlight, friction and sweat.
• 5.It should not change colour, nor bleach out on the application of toilet preparations
such as setting lotion, hair waving preparation, soap or shampoo etc.
• 6.Colourants should be stable over time in the aqueous solutions and formulated
products in forms in which they are sold and used.
• 7.It should not produce different colouration on different parts of the same hair.
• 8.It should have affinity for Hair Keratin and capacity to penetrate into the hair shaft.

57
 58

HAIR
COLORANTS
• RAW MATERIALS
• Differ from manufacturer to manufacturer. But in
general, hair dyes include:
• – modifiers,
• – antioxidants,
• – alkali,
• – soaps,
• – ammonia,
• – wetting agents,
• – fragrance,
HAIR COLORANTS
• RAW MATERIALS
• A variety of other chemicals used in small
amounts that impart special qualities to hair
(such as softening the texture) or give a
desired action to the dye (such as making it
more or less permanent).
• Dye chemicals are usually amino
compounds.
• Other chemicals used in hair dyes act as
modifiers, which stabilize the dye pigments or
otherwise act to modify the shade.

59
HAIR COLORANTS
• RAW MATERIALS
• The modifiers may bring out color tones,
such as green or purple, which complement
the dye pigment. e.g. resorcinol
• Antioxidants protect the dye from oxidizing
with air. Most commonly used is sodium
sulfite.
• Alkali are added to change the pH of the dye
formula, because the dyes work best in a
highly alkaline composition. Ammonium
hydroxide is a common alkali.

60
61

TYPES OF HAIR
COLORANT
• Temporary Hair Color
• Temporary hair color is available in
various product forms including rinses,
shampoos, gels, sprays, foams.
• This type of hair color is typically used
to give brighter, more vibrant shades or
colors such as orange or red, that may
be difficult to achieve with semi-
permanent and permanent hair color.
 62

TYPES OF HAIR
COLORANT
• Temporary Hair Color
• While temporary hair color products hold a
lesser market than semi- permanent and
permanent agents, they have value in that
they can be easily and quickly removed
without bleaching or application of a different
coloring product.
• These colorants do not penetrate into cortex
or medulla.
• As such the dye is easily removed with
shampoo so known as temporary hair color
 63

TYPES OF HAIR
COLORANT
• Semi-Permanent Hair Color
• Give stronger & more permanent
coloration to hair than temporary hair
colorant
• Some colors are removed in 4-8
shampooings.
64

TYPES OF HAIR
COLORANT
• Semi-Permanent Hair Color
• Dyes used are:
• – Ntirophenyledenediamine,
• – Nitroaminopheols,
• – Aminoanthraquinones.
• Mixture is prepared before preparing
color shades.
• Should be studied on white wool or hair.
• Semi hair color has no Ammonia.
TYPES OF HAIR
COLORANT
• Permanent Hair Color
• All "permanent" haircolor products and
lighteners contain both a developer, or
oxidizing agent, and an alkalizing
ingredient as part of their ammonia or an
ammonia substitute.
• The purpose of this is to:
• – raise the cuticle of the hair fiber so the
tint can penetrate,
• – facilitate the formation of tints within
the hair fiber,
• – bring about the lightening action of
peroxide.

65
TYPES OF HAIR
COLORANT
• Permanent Hair Color
• When the tint (color) containing the alkalizing ingredient
is combined with the developer (usually hydrogen
peroxide), the peroxide becomes alkaline and diffuses
through the hair fiber, entering the cortex, where the
melanin is located.
• The lightening occurs when the alkaline peroxide
breaks up the melanin and replaces it with new color.
 • Hair care product
performance and safety
ultimately determine
product success and
longevity. For best
market results, precisely
planned performance
and safety evaluations
are required.
• Moreover, international
regulatory agencies
require a demonstration
of product safety to
ensure that new-to-
market products will not
SAFETY AND EVALUATION: pose health risks or
harm to consumers.
HAIR CARE PRODUCTS
67
 SAFETY AND EVALUATION: HAIR CARE PRODUCTS

Phases of comprehensive hair care

product performance testing :
Phase I: Pre-Clinical Testing
Because hair care products will contact the
skin and hair and will likely contact the
eyes, pre-clinical dermal and ocular
toxicity and irritation testing is required
early in the safety evaluation process.

68
SAFETY AND EVALUATION: HAIR CARE
PRODUCTS
• Phases of comprehensive hair care
product performance testing :
• Phase II: Clinical Study Data
Collection and Evaluation
• Panelists are recruited and
scheduled according to the initial
study design and timeline.
• Clinical data can vary in type,
complexity, and collection intervals.
PHASE II HAIR
PRODUCT
PERFORMANCE
TESTS

• a) Trichological (Hair
Count) Analysis.
• The trichological analysis
determines changes in hair
growth patterns. During
this test, a trained
professional uses a
dermascope or videoscope
to survey the scalp and
record changes in
observed hair growth
patterns.

70
PHASE II HAIR
PRODUCT
PERFORMANCE
TESTS

• b)Traction Test.
• The Traction Test also known
as Gravimetric “Pull” Analysis,
“Sabouraud’s sign,” or “the pull-
out sign” is used to measure
hair shedding patterns.
• Prior to shampooing, 20-60
strands of subjects’ hair are
grasped at the base of the
strands and tugged firmly away
from the scalp. Active hair
shedding is indicated by pulling
more than 10% of strands from
the scalp.
71
PHASE II HAIR
PRODUCT
PERFORMANCE
TESTS

• c)Hair Pluck” Test.

• The “Hair Pluck” Test
evaluates changes in
hair growth cycles and in
hair breakage over time
using hair shafts
“plucked” from the scalp.

72
PHASE II HAIR PRODUCT
PERFORMANCE TESTS

• d)Regimented Combing
Technique.
• The Regimented Combing
Technique is used to assess
changes in hair fallout rates.
For this test, panelists are
asked to use a specific
combing technique to
evaluate hair fallout rates.
•
73
PHASE II HAIR PRODUCT
PERFORMANCE TESTS • e)Tensile Test.
• Tensile Tests measure
any alterations in hair
strength and resilience.
Hair tensile strength is
measured using the Dia-
Stron Mini Tensile Tester
(MTT). The MTT device
uses 3-point bending and
torsion tests to measure
the force overtime
required to elongate and
break a strand of hair.

74
*kin )are Products

75
SKIN
Skin is the outer covering
of the body and is the
largest organ of the
integumentary system.
76
 • Biology of the Skin:
• Glabrous skin, found on the palms and
soles of the feet, lacks hair follicles and
sebaceous glands but has a very thick
epidermis and encapsulated sense
organs in the dermis.
SKIN • In hairy skin, hair follicles and
sebaceous glands are both present, but
there are no encapsulated sensory
organs. Facial skin has large sebaceous
glands associated with fine vellus hairs,
contrasting sharply with the scalp, which
contains large hair follicles.

77
78
 SKIN
FUNCTIONS OF THE
SKIN:
1. Protection
2. Vitamin D production
3. Sensation
4. Excretion
5. Body temperature
regulation

79
EPIDERMIS
• The epidermis is an avascular structure, made
up of many layers of cells.
• The special structure of the epidermis is
classified as stratified squamous epithelium
and is typical of vertebrate animals.
• It is responsible for producing the main barrier
known as the horny layer or stratum corneum,
which forms the outermost part of the
epidermis.
• The horny layer is made up of water-resistant
dead cells, called corneocytes, which are
segmented together with a complex lipid
material.

80
EPIDERMIS

◉ The lower living layers of the

epidermis can also be
subdivided as follows:
1.the germinative or basal layer;
2.the stratum spinosum or prickle
cell layer;
3.the stratum granulosum or
granular layer, which is
characterized by the presence of
distinctive keratohyalin granules.

81
DERMIS

• The dermis functions as a

supporting frame to the
epidermis, supplying it with
nutrients via the blood
capillaries. It also supports
the sensory nervous
system, secretory glands
and hair follicles.
• Unlike the epidermis, which
is a cellular structure, the
underlying dermis consists
of connective tissue.

82
Compositions of Dermis:
1. Collagen and elastin
◉ Collagen forms the major constituent of the fibrous protein which gives
the skin its tensile strength.
2. Ground substance
◉ The dermal ground substance consists of salt, water and
glycosaminoglycans. The latter form complexes with protein molecules
known as proteoglycans.
3. Mast cells.
◉ The mast cells, which are the second major cell type in the dermis, can be
found close to the small blood vessels.
4. Sweat glands.
5. Sensory skin receptors

83
HYPODERMIS

• Below the epidermis is a layer of fatty

or adipose tissue called the
hypodermis.
• The cells in this layer synthesize and
store fat as an energy reserve. This is
to help insulate the body from low
external temperatures and to act as a
buffer against trauma.
• On a more familiar note, the
hypodermis provides the body with its
contours, whether they are attractive
curves or unwelcome bulges.

84
SKIN TYPES

• 1. Normal – soft smooth skin with a healthy

appearance
• 2. Oily – shiny with enlarged pores. Often
blemished
• 3. Dry – fine texture, flaky, many expression
lines, poor elasticity
• 4. Sensitive – florid with broken capillaries, fine
textured, like dry skin
• 5. Blemished – excessively oily with blemishes

85
TYPES OF SKIN CARE
PRODUCTS
• 1.Cleansers
• is a facial care product that is used to remove
make-up, dead skin cells, oil, dirt, and other
types of pollutants from the skin of the face.
This helps to unclog pores and prevent skin
conditions such as acne.
• A cleanser is the first step in a skin care
regimen and can be used in addition of a toner
and moisturizer, following cleansing.

86
Using a cleanser designated for the facial skin to remove dirt is
considered to be a better alternative to bar soap or another form of
skin cleanser not specifically formulated for the face for the following
reasons:
◉ Bar soap has an alkaline pH (in the area of 9 to 10), and the skin's surface pH is on
average 4.7. This means that soap can change the balance present in the skin to favor
the overgrowth of some types of bacteria, increasing acne. In order to maintain a
healthy pH balance and skin health, your skin must sit on the proper pH level.
◉ Bar cleansers have thickeners that allow them to assume a bar shape. These
thickeners can clog pores, leading to acne.
◉ Using bar soap on the face can remove natural oils from the skin that form a barrier
against water loss. This causes the sebaceous glands to subsequently overproduce
oil, a condition known as reactive seborrhoea, which will lead to clogged pores.In
order to prevent drying out the skin, many cleansers incorporate moisturizers.

87
FACE CLEANSERS

a) Cream b) Foam c) Oil

cleansers cleansers cleansers

d) Clay e) Micellar f) Powder

cleansers cleansers cleansers

h) Cleansing
g) Bar mitts / clothes / i) Charcoal
cleansers cleanser
wipes

j) Honey k) Vitamin C
Cleanser Cleanser

88
TYPES OF SKIN CARE
PRODUCTS

2. Exfoliator
• Exfoliating is the process of removing dead skin
cells from the surface of your skin using a
chemical, granular substance, or exfoliation tool.
• Your skin naturally sheds dead skin cells to make
room for new cells every 30 days or so. But
sometimes, dead cells don’t shed completely. This
can result in dry, flaky patches and clogged pores.
Exfoliating can help prevent this.

89
TYPES OF EXFOLIATION

Mechanical
- This process involves physically scrubbing the skin
with an abrasive.
- Mechanical exfoliants include microfiber cloths,
adhesive exfoliation sheets, micro-bead facial scrubs,
crepe paper, crushed apricot kernel or almond shells,
sugar or salt crystals, pumice, and abrasive materials
such as sponges, loofahs, and brushes.
- People with dry skin should avoid exfoliants which
include a significant portion of pumice, or crushed
volcanic rock.

90
TYPES OF 91
EXFOLIATION

• Chemical
• - Chemical exfoliants include scrubs containing
salicylic acid, glycolic acid, fruit enzymes, citric acid,
or malic acid which may be applied in high
concentrations by a medical professional, or in lower
concentrations in over-the-counter products.
• - Chemical exfoliation may involve the use of
products that contain alpha hydroxy acids (AHAs),
beta hydroxy acids (BHAs), or enzymes that act to
loosen the glue-like substance that holds the cells
together, allowing them to ease away.
TYPES OF SKIN
CARE PRODUCTS
3.Treatments
• - are used to address specific skin
concerns such as acne, dark spots,
hyperpigmentation, fine lines and
inflammation. Skin treatment
products are all regulated and have
to be approved by the FDA. They can
be in the forms of creams, gels,
lotions, solutions, serums and
medicated facial pads.

92
 TYPES OF SKIN
CARE PRODUCTS
4. Serums
• - Serums usually contain antioxidants,
which help fight free radical damage.
• - They can also contain anti-aging
ingredients such as retinols and peptides,
which stimulate collagen production.
• - Because they penetrate deep into the
skin, these products are great for hydrating
dry skin.
• - They are best used after your cleanser,
and they can be used underneath
moisturizer to treat the skin while sleeping.

93
TYPES OF SKIN
CARE PRODUCTS
5. Sunscreen
- is a lotion, spray, gel, foam, stick or other
topical product that absorbs or reflects some of
the sun's ultraviolet (UV) radiation and thus
helps protect against sunburn.
- Diligent use of sunscreen can also help to
slow or temporarily prevent the development of
wrinkles, dark spots and sagging skin.

94
TYPES OF
SUNSCREEN
a) Physical Sunscreen
• stay on the surface of the skin and
mainly deflect the UV light.
Examples:
• i. Zinc oxide - an opaque, full-
spectrum sunscreen also used to give
opacity to face powder and foundation.
• ii. Titanium dioxide - a full-spectrum ,
which means that it protects the skin
from both UVA and UVB rays. It is also
used to give opacity to face powder,
eye shadow, and foundation.

95
TYPES OF
SUNSCREEN
b) Chemical Sunscreen
• which absorb the UV light.
• Example: UV organic filters
TYPES OF SKIN
CARE PRODUCTS
6.Chemical Peel
• remove the outer layer of the skin, which
means they tend to go deeper to remove
more excess dead skin cells than
exfoliators.
• They usually contain glycolic, salicylic or
lactic acids.

97
TYPES OF SKIN CARE
PRODUCTS
7.Toner
• it shrinks pores and restores skin to its natural pH
balance.
• this is important because when our pH levels are
thrown out of whack due to soaps and chemicals in
cleansers, oil production increases, causing a cycle of
breakouts.
• can be used after a cleanser twice a day to remove
excess traces of makeup or other residue from the skin.
TYPES OF SKIN
CARE PRODUCTS
8.Moisturizer
A product that adds water, and often some
emollients, to the skin. A variety of types of
moisturizers are available (for various skin
types), and are necessary for all skin types to
prevent dehydration.
Replaces water lost from the skin
- Dryness and flexibility cannot be corrected
with oils - Only Water
- Oil is used to limit the evaporation of water.

99
 INGREDIENTS OF
MOISTURIZERS
a) Humectant - An ingredient in skin or hair products that
draws moisture from the air to moisturize the skin and also
promotes the retention of moisture in the skin
Examples:
• Glycerine
• Propylene glycol
• Sorbitol
• Urea
• Lactic acid
• Hyaluronic Acid

100
INGREDIENTS OF MOISTURIZERS
b) Emollient - Supple, waxlike, lubricating, thickening
agents that prevent water loss and have a softening
and soothing effect on the skin.
- A skin conditioning agent which helps maintain the
smooth, soft pliable appearance of the skin.
- Usually a grease or an oil that softens the skin and
protects it from dryness.
Examples:
• Sunflower seed oil Olive oil
• Allantoin Cocoa butter
• Myristyl Myristate Mineral oil
101
INGREDIENTS OF MOISTURIZERS

c) Occlusives - substances that hold strongly to

the surface of the skin, preventing access to the
air and increasing absorption of cosmetic
treatments.
- Usually refers to an occlusive shield or film
that is spread onto the skin to slow or prevent
moisture evaporation.
Examples:
Petrolatum
Lanolin
Candililla wax
Dimethicone
102
SAFETY AND EVALUATION:
SKIN CARE PRODUCTS

• One of the skin’s primary physiological

functions is to act as the body’s first line of
defense against exogenous agents.
• However, the skin should not be viewed
as a flawless physicochemical barrier.

103
SAFETY AND EVALUATION: SKIN CARE
PRODUCTS
• Many low–molecular weight
compounds are capable of
penetrating this barrier. When toxic
agents (such as irritants or
allergens in cosmetic products)
permeate it, the resulting adverse
effects may cause considerable
discomfort to the consumer.
• Even minor disturbances of the skin
surface can produce discomfort,
especially in the facial area which
has an extensive network of
sensory nerves.
TYPES OF
COSMETICS ALLERGIC
REACTION

1. CONTACT DERMATITIS
• This is a nonspecific term
used to describe any
inflammatory skin disease
resulting from contact with
an irritant or allergenic
substance.
• Whatever the causative
agent, the clinical features
are similar: itching,
redness, and skin lesions.

105
TYPES OF CONTACT
DERMATITIS
• A. IRRITANT CONTACT DERMATITIS
(IRRITATION)
• It is a term given to a complex group of localized
inflammatory reactions that follow
nonimmunological damage to the skin.
• The inflammation may be the result of an acute
toxic (usually chemical) insult to the skin, or of
repeated and cumulative damage from weaker
irritants (chemical or physical).
• There is no definite laboratory test for ICD—
diagnosis is by clinical morphology, of course,
and appropriate negative patch-test results.

106
Categories of ICD:
Acute Irritant Contact Dermatitis
Ø Acute ICD is the result of a single overwhelming exposure to a strong irritant or
a series of brief physical or chemical contacts, leading to acute inflammation of
the skin.
Cumulative Irritant Contact Dermatitis
Ø Cumulative irritant contact dermatitis or chronic ICD develops as a result of a
series of repeated and damaging insults to the skin. The insults may be
chemical or physical.
Delayed Acute Irritant Contact Dermatitis
Ø Some chemicals produce acute irritation in a delayed manner so that the signs
and symptoms of acute irritant dermatitis appear 12 to 24 hours or more after
the original insult.

107
TYPES OF CONTACT
DERMATITIS
• B. ALLERGIC CONTACT DERMATITIS
• ACD occurs when a substance comes into
contact with skin that has undergone an
acquired specific alteration in its reactivity
as a result of prior exposure of the skin to
the substance eliciting the dermatitis.
• The skin response of ACD is delayed,
immunologically mediated (Type IV), and
consists of varying degrees of erythema,
edema, papules, and papulovesicles.
• Patch testing is the gold standard.

108
TYPES OF CONTACT
DERMATITIS
• C. PHOTOIRRITANT CONTACT
DERMATITIS
• It is a chemically induced
nonimmunological skin irritation requiring
light. This reaction will occur in all
individuals exposed to the chemical–light
combination.
• Bergapten, a component of bergamot oil,
is a potent photoirritant that causes
berloque dermatitis.

109
TYPES OF CONTACT
DERMATITIS
• D.PHOTOALLERGIC CONTACT DERMATITIS
• It is an immunological response to a substance
that requires the presence of light.
• The substance in the skin absorbs photons and is
converted to a stable or unstable photoproduct,
which binds to skin proteins to form an antigen,
which then elicits a delayed hypersensitivity
response.
• Examples of photoallergens present in cosmetics
are musk ambrette and 6-methylcoumarin, which
are present in fragrances.

110
TYPES OF COSMETICS
ALLERGIC REACTION
• 2.CONTACT URTICARIA SYNDROME
• It represents a heterogeneous group of
inflammatory reactions that appear,
usually within a few minutes to an hour,
after contact with the eliciting substance.
• Clinically, erythematous wheal-and-flare
reactions are seen, and sensations of
burning, stinging, or itching are
experienced.
• Diagnosis may be achieved by a variety
of skin tests—the open test is the
simplest of these and is the ‘‘first-line’’
test.

111
 i. Nonimmunological ii. Immunological
Contact Urticaria Contact Urticaria
◉ It is the most ◉ These are
common class of immediate (Type I)
CUS. The reaction allergic reactions in
usually remains people who have
TYPES OF localized. previously been
sensitized to the
CONTACT ◉ Examples of causative agent.
URTICARIA cosmetic substances
known to produce ◉ ICU is IgE mediated
SYNDROME NICU are and is more
preservatives (e.g., common in atopic
benzoic acid and individuals. Food
sorbic acid) and substances are
fragrances (e.g., common causes of
cinnamic aldehyde) ICU.
TYPES OF COSMETICS
ALLERGIC REACTION

• 3. ACNEGENICITY
• This refers to the capacity of some agents
to cause acne or aggravate existing acne
lesions.
• This term may be subdivided to include
comedogenicity and pustulogenicity.

113
TYPES OF i.Comedogenicity
ACNEGENICITY ◉ This is the capability of an agent to cause
hyperkeratinous impactions in the
sebaceous follicle, or the formation of
microcomedones, usually in a relatively
short period of time.

ii.Pustulogenicity
◉ This refers to the capability of an
agent to cause inflammatory papules
and pustules, usually in a relatively
short period of time.
114
SAFETY AND
EVALUATION: SKIN
CARE PRODUCTS
• Factors Contributing to Contact Allergic
Reactions to a Cosmetic Product
• Frequency of Use
• Composition
• Concentration of Ingredients
• Purity of Ingredients
• Common Use of Cosmetic Ingredients in
Pharmaceuticals
• Cross-Sensitivity
• Penetration-Enhancing Substances
• Application Site
• Condition of the Skin
• Contact Time

115
SAFETY AND EVALUATION:
SKIN CARE PRODUCTS

• Common Components that cause Cosmetic

Allergic Reaction:
• Fragrance Ingredients
• Preservatives
• Antioxidants
• ‘‘Active’’ or Category-Specific Ingredients
• Excipients and Emulsifiers
• Coloring Agents

116
 • International regulatory agencies require that skin care products
PRODUCT available on the market do not cause damage to human health when
applied under normal and reasonably foreseeable conditions of use.

SAFETY TESTING • Adequate information must be readily available to demonstrate

product safety and this information should be keep on file with all
other studies supporting performance product claims.
117
 PRODUCT SAFETY TESTING

◉ Such safety information could be based on the individual toxicity of

ingredients but testing the final product is important and pertinent
particularly in the following cases:
ü A new ingredient known to cause slight
eye or skin irritation is present
ü Significant modifications of the
formulation have been made;
ü The vehicle used in the formulation
results in significantly greater skin
penetration
ü Interaction between ingredients is likely
to result in the formation of a new,
potentially toxic or irritant substance
ü There is a specific safety claim
118
 TYPES OF SAFETY ASSESSMENT

1. PATCH TEST
Ø a test for determining allergic sensitivity
that is made by applying to the unbroken
skin small pads soaked with the allergen
to be tested
Ø The 48-hour patch test allows the
assessment of the primary irritation
potential of a topical product.
Ø The test is conducted on a panel of at
least 25 subjects. The patches used can
be occlusive or semi-occlusive
depending on the nature of the product.

119
 TYPES OF SAFETY ASSESSMENT

2. Human Repeat Insult Patch

Test (HRIPT)
Ø a test for determining the irritation
and/or sensitization potential of a test
material(s), in support of sensitive skin
claims, after repeated application under
occlusive or semi-occlusive patches to
the skin of human subjects.
Ø The HRIPT consists of 2 phases, and
sometimes 3.

120
 TYPES OF SAFETY ASSESSMENT

3. NON-COMEDOGENIC TEST
Ø a test to evaluate the skin condition
before and after one month of product
usage. The evaluator counts the number
of comedons and blackheads on the
forehead, cheeks and chin.
Ø Alternatively, a non-comedogenic claim
can be assessed via a microscopic
examination of the skin after application
of patches containing the product.

121
 TYPES OF SAFETY ASSESSMENT

4. NON-ACNEGENIC TEST
Ø a test to evaluate skin condition
before and after one month of
product usage. The evaluator
counts the number of acne
lesions (papules and pustules) on
the forehead, cheeks and chin.

122
 TYPES OF SAFETY ASSESSMENT

5. PERIOCULAR TOLERANCE TEST

Ø a test that allows to assess the irritation potential of a topical product applied
on the eye contour area.
Ø The study is conducted under the supervision of an ophthalmologist. The
condition of the eye and around the eye area is examined before and after a
given period of product usage.

123
 REferences

◉ Barel A., Paye M. and Maibach H.

(2009). Handbook of Cosmetic
Science and Technology, 3rd ed. New
York: Informa Healthcare USA, Inc.
◉ Butler, K. (2000). Poucher’s Perfumes,
Cosmetics, and Soaps 10th ed. Great
Briatain; Kluwer Academic Publishers.

124
 REferences

◉ ASEAN Cosmetic GMP

◉ Barel A., Paye M. and Maibach H. (2009).
Handbook of Cosmetic Science and Technology,
3rd ed. New York: Informa Healthcare USA, Inc.
◉ Butler, K. (2000). Poucher’s Perfumes, Cosmetics,
and Soaps 10th ed. Great Briatain; Kluwer
Academic Publishers.

125
OUR LADY OF FATIMA UNIVERSITY
College of Pharmacy
PHARMACEUTICAL SEMINAR 2

PHARMACEUTICAL
COSMETICS
(PART 2)
 UNIT OUTCOMES

At the end of this unit, the students are

expected to:
◉Demonstrate familiarity on cosmetic science
terminologies.
◉Demonstrate knowledge on the principles
and methods involved in formulation of
cosmetic products the science of cosmetics
◉Describing the GMP requirements for
cosmetics.
◉Identify the requirements for cosmetic
notification.

2
 checklist

◉ Read unit outcomes and unit objectives

◉ Read course guide prior to class
attendance
◉ Proactively participate in discussions
◉ Watch videos related to the topic
◉ Participate in discussion board (Canvas)
◉ Answer and submit course unit tasks

3
Required Readings

◉ Baki, G., & Alexander, K. S. (2015).

Introduction to Cosmetic
Formulation and Technology. New
Jersey, USA: John Wiley & Sons.
◉ Iwata, H., & Shimada, K. (2013).
Formulas, Ingredients and
production of Cosmetics. Tokyo,
Japan: Springer Japan.
◉ Tadros, T. F. (2016). Formulations: In
Cosmetic and Personal Care. Berlin:
de Gruyter Publisher.

4
WHAT IS ORAL
HYGIENE? ◉ Oral hygiene is the practice of
keeping the mouth and teeth
clean to prevent dental
problems, most commonly,
dental cavities, gingivitis,
periodontal (gum) diseases
and bad breath.
 The purpose of oral hygiene is to prevent
the build-up of plaque, the sticky
substance formed by the attachment of
PURPOSE bacteria coating that adheres to the
pellicle, which is a thin acellular,
OF ORAL glycoprotein.

HYGIENE
Plaque, when not removed within 24
hours, forms a substance called calculus
or tartar. Plaque calcifies when calcium
salt precipitates from the saliva.
 ◉ The formation of caries (tooth decay) is
attributed to the action of acids obtained
from oral bacterial metabolism of dietary

ANTICARIES carbohydrates. The build-up of plaque on the

tooth surface usually aids the decay process
by forming pockets or crevices on the teeth

AGENTS
surface.

◉ Brushing removes material from tooth before

it hardens into calculus.
 APPROACH TO CARIES
PREVENTION:

Ø Flossing
Ø Brushing

*accompanied by fluoride
administration either given
internally or topically to the
teeth
 Oral Hygiene Product

Dentrifices
◉ Products that enhance the removal of stains and plaque by the
toothbrush.
1. Toothpastes
2. Mouthwashes
3. Cosmetic whitening products
4. Mouth/Breath Spray
5. Fluoride gel
 Toothpastes

◉ Used to decrease the incidence of dental caries, reduce

mouth odors, and enhance personal appearance.
◉ Brush with soft toothbrush for 2 minutes. No RINSING,
EATING, or DRINKING for 20 minutes.
◉ Most common ingredients:
○ Abrasives – responsible in removing plaque. Ex.
Silicates, sodium bicarbonate, dicalcium
phosphate, sodium metaphosphate, calcium
pyrophosphate, calcium carbonate, magnesium
carbonate, and aluminum oxides. High-abrasive
formulations are not advisable for long-term use
as it may lead to eventual exposure to root
surfaces.
 Toothpastes

◉ Used to decrease the incidence of dental caries, reduce mouth odors, and
enhance personal appearance.
◉ Most common ingredients:
○ Surfactants – foaming agents that aid in the removal of debris. Most
frequently used are sodium lauryl sulfate and sodium dodecyl
benzene sulfonate.
○ Humectant – prevents the drying of the preparation. Ex. Sorbitol,
glycerin, and propylene glycol.
○ Suspending agents – add thickness to the formulation. Ex.
Methylcellulose, tragacanth, karaya gum.
○ Flavoring agents – sorbitol or saccharin
 ◉ Used to decrease the incidence of dental caries, reduce
mouth odors, and enhance personal appearance.
◉ Most common ingredients:
○ ■ Special ingredients:

Toothpastes
Pyrophosphates – for tartar-control; retard
the formation of tartar. However, they form
an alkaline solution that can irritate skin and
which is most often exhibit by rash around
the mouth.
■ Fluoride – anticariogenic; replaces the
hydroxyl ion in hydroxyapatite with the
fluoride ion, forming fluoroapatite on the
surface of the enamel and hardens it,
leading to a more acid-resistant enamel.
■ Triclosan – antimicrobial agent which helps
prevent gingivitis, plaque, cavities, and tartar.
■ Desensitizing agents – reduce pain in
sensitive teeth. Ex. 5% potassium nitrate
 ◉ Rinse two times a day with a capful. Rinse for
1 minute and spit. If used in conjunction with
the toothpaste use the rinse first, then brush.
◉ May contain astringents, demulcents,
detergents, flavors, germicides, and fluoride.
○ Cosmetic mouthwashes – to freshen
breath; nontherapeutic and no antiseptic
Mouthwashes/ Oral property. Classified based on
Rinses ingredients, alcohol content, and
appearance.
○ Antiplaque mouth rinses – claim to
prevent formation of tartar, having the
same ingredients as tartar-control
toothpaste. Ex. Cetylpyridium chloride,
chlorhexidine (staining is associated with
the overuse of these two ingredients)
 Cosmetic Whitening Product

◉ CARBAMIDE PEROXIDE 10%

◉ It is a tooth whitener, carbamide peroxide, a mild anti-septic,
also called urea hydrogen peroxide, perhydrit, hyperol, or
perhydol, is an addition complex of hydrogen peroxide with
urea, which has a mild effect.
◉ Reacts with water in saliva, carbamide peroxide dissociates to
hydrogen peroxide (34%) & urea.
◉ Haywood and Heymann introduced bleaching of teeth with
10% carbamide peroxide gels placed in custom-built trays to
be worn by patients at night for 2-6 weeks.
 Cosmetic Whitening Product

◉ HYDROGEN PEROXIDE
◉ Active ingredient in some cosmetic whiteners in gel or liquid form.

Possible risk in using cosmetic whitening products:

◉ Alteration of normal flora
◉ Tissue damage
◉ Tooth sensitivity
◉ Gingivitis
◉ Potentiation of carcinogenic effects of other agents
 Fluoride gel

◉ Prescribed high-concentrated topical agent (1-2%)

intended either for professional applications in
plastic/disposal trays 2- 4 times per year or self-applied
with aid of a toothbrush once or twice per week.
◉ The formulations are based on sodium fluoride,
acidulated phosphate fluoride or amine fluoride. The
gels are flavored but contain no abrasive cleaning
agents or preservatives.
 FLUORIDE’S ACTION IN INHIBITING CARIES

a) Fluoride decreases the solubility of enamel in acid

b) Fluoride has enzyme inhibitory properties

◉ Oral route places fluoride into systemic circulation

allowing fluoride to laid down in unerupted teeth
as they are formed.
SPECIFIC INGREDIENTS
 SODIUM FLOURIDE USP

PROPERTIES:
◉ Occurs as a white, odorless powder which is soluble in water
and insoluble in alcohol
USES:
◉ Officially used as dental prophylactic
○ 2% aqueous sol’n is widely used topically. Usual
procedure is a series of 4 treatments: beginning at the age
of 3; ages 7, 11 and 13 as the permanent teeth erupts
 STANNOUS FLOURIDE USP

SYNONYM: Tin Diflouride

PROPERTIES:
◉ Stannous fluoride occurs as a white crystalline powder and
has a bitter salty taste. It melts at about 213 degrees Celsius;
◉ Freely soluble in water; insoluble in alcohol, ether and
chloroform
 STANNOUS FLOURIDE USP

USES:
◉ extensively used for topical fluoride application
○ A simple application of a freshly prepared 8% solution at 6
to 12 months intervals is used
◉ it requires only 1 application per treatment as compared to a
series of 4 application per treatment of NaF
○ solution is applied to a cleaned, dry teeth.
v PUMICE USP
SYNONYMS: Pumice Stone; Piedra Pomez
PROPERTIES:
◉ substance of volcanic origin; consisting chiefly of complex
silicates of aluminum, potassium and sodium
◉ occurs as very light, hard, rough, porous grayish masses, or
as a gritty gray powder
v PUMICE USP
PROPERTIES:
◉ Pumice is odorless and
tasteless; stable in air;
practically insoluble in water
and is not attacked by acids.
 GRADES OF
FINENESS:
1. Pumice flour or superfine
2. Fine Pumice
3. Coarse pumice

USE: Dental Abrasive

 ◉ “mottled enamel”
◉ too much fluoride present in the
tissue fluids
○ teeth is chalky and soft
DENTAL ◉ occurs in areas where the fluoride
concentration of drinking water
FLUOROSIS exceeds 2 ppm
◉ only occurs during excessive
ingestion of fluoride during the
period of teeth development
LETHAL ADULT DOSE OF FLUORIDE:
2 -5 g
FLUORIDE
TOXICITY
q ACUTE
SYSTEMIC
TOXICITY
◉ FLUORIDE TOXICITY
◉ Maximum Permitted Concentration of Fluoride in toothpaste for
◉ OTC sales – 0.15%
◉ Pharmacies – 1.3%
◉
◉ The Probable Toxic Dose (PTD) of fluoride, 5 mg F/kg of body weight.

◉ SAFETY PRECAUTIONS:
◉ Package size & especially, fluoride contents be controlled.
◉ Supervised toothpaste use by preschool children
◉ Manufacturers should be encouraged to include this advice in labels.
FLUORIDE TOXICITY CHRONIC TOXICITY
EPIDEMIOLOGICAL EVIDENCE
LOCAL TOXICITY

1. MECHANICAL ABRASION

ABRASIVES: Essential component of toothpastes

mechanical removal of stained tooth pellicle.
-Requirements of in vitro study

Use a relevant substrate (natural teeth, dentine)

Knowledge of the abrasive compound + Abrasive particle size

& other constituents of the toothpaste.
-The method of brushing (e.g. horizontal brushing)

-The abrasivity of all commercially available toothpastes is

generally low to no clinical significance.
◉ 2. SOFT TISSUE REACTION
◉ Acute Reactions Of The Oral Soft Tissues To Oral Hygiene Products
○ Epithelial Peeling
○ Mucosal Ulceration & Inflammation
○ Gingivitis
○ Petechiae
◉ Patients may complain of
○ A Burning Or Stinging Sensation
○ Soreness Or Pain
○ Staining Of The Teeth And Tongue
LOCAL REACTIONS TO ANTIMICROBIAL AGENTS

Chlorhexidine Mouthwash
• Brown discoloration of the teeth and tongue and with altered taste sensation
• Superficial desquamation of the oral mucosa.
Benzethonium chloride (0.2%)
• Caused desquamative lesions of the oral mucosa in 4 out of 5 subjects
• Discoloration of the tongue and around some of the teeth in 8 out of 12 subjects
Cetylpyridinium chloride – rinse à burning sensation
D!"#$A%&'!("#)*!%&"(P$#DU"%)

33
34

DECORATIVE
COSMETIC PRODUCTS

• Decorative cosmetics, for skin, hair and

other appendages, e.g. lips and nails, can
be divided into those which aim to:
• Improve and/or protect and maintain
good health
• Enhance and change appearances
and at the same time cover up
defects.
 DECORATIVE COSMETIC PRODUCTS

The formulation of the finished products starts with a clear understanding of the target
consumer requirements and any product claims that the marketing department wish to
make.
These considerations could be:
◉ Performance
◉ User type
◉ Usage instructions
◉ Method of application
◉ Type of packaging that will hold
the product.
35
TYPES OF DECORATIVE
COSMETIC PRODUCTS

• A. Facial Make-Up
• Facial Makeup Products are
products that are used to color
and highlight facial features.
They can either directly add or
alter color or can be applied over
a foundation that serves to make
the color even and smooth.

36
INGREDIENTS OF
FACIAL MAKE-UP

• 1.Talc
• It is the main component of face
powders; in some products it could
comprise up to 70% or 75% of the
formulation.
• Talc is used mainly because of
outstanding spreadability (slip) and low
covering power (translucency).
• Grades of talc should be judged on slip,
smoothness, fineness, grit, density,
colour and odour. In addition a check
should be made for impurities such as
carbonates and water-soluble iron and
the talc must be free from asbestos.

37
INGREDIENTS OF
FACIAL MAKE-UP
• 2.Kaolin
• Also known as 'China clay', a naturally
occurring compound, is a hydrated aluminium
silicate.
• There are three different groups of clays
(kaolinite, nacrite and dickite) having
essentially the same formula (Al2O3 • 2SiO2
• 2H2O) that are classified as kaolin.
• It is almost white in colour. It has less slip
than talc, and the product can end up with a
harsh feel.

38
INGREDIENTS OF
FACIAL MAKE-UP

• 3.Zinc Oxide
• It is occasionally used at moderately low levels in
face powders because it has quite good covering
power, is slightly astringent and a recognized skin
protectorant; it therefore imparts soothing
properties to the skin.

39
INGREDIENTS OF
FACIAL MAKE-UP
• 4.Calcium Carbonate
• Also known as ‘Precipitated
Chalk’, Calcium Carbonate is a
mildly alkaline, white, odourless
microcrystalline powder available
in special grades with differing
particle sizes and densities.
• It is mainly used because of its
excellent absorption
characteristics. It is matte and
can give a 'bloom' effect to the
coating on the face.

40
INGREDIENTS OF FACIAL MAKE-UP

• 4.Calcium Carbonate
• As a material, it has good absorption
characteristics and, like kaolin, it may
also be used to remove some of the
inherent shine of talc.
• Excessive use is not recommended
(greater than 15%) because of its
undesirable dry powdery feel and
adverse effect on the slip of the
product.
Other important ingredients of
Facial Make-Ups:
◉ Magnesium carbonate
◉ Metallic soaps
◉ Starches
◉ Walnut flour
◉ Micronized plastics
◉ Mica
◉ Fumed silica
◉ Colorants
◉ Preservatives
◉ Fragrances

42
TYPES OF FACIAL
MAKE-UP
• I.Foundation Make-Up
• These are used to unify the colour of the skin, to
cover blemishes and skin defects and to provide a
basis for further enhancement by the application of
lip and eye colour cosmetics.
• Many of these modern types are also used for their
skin-care benefits, with additions such as
sunscreens, natural extracts and vitamins, so that
with pigmented products the consumer applies
colour whilst looking after her skin.

43
FORMS OF
FOUNDATION
• Cake foundation make-up
• It was modified and developed from that
used in the theatre and film industries.
• The professionals used stick make-up
which became Max Factor's Pan Sticks,
the first products to become commercially
available.
• They were a mixture of talc, kaolin,
magnesium carbonate, titanium dioxide
and iron oxides added to molten waxes
and oils.

44
FORMS OF FOUNDATION

• Liquid foundation make-up

• These are a suspension of pigments in an emulsion
base, the same types as those used for facial
moisturizers.
• Traditionally they were based on either anionic or
cationic emulsification systems.
• The major components of this type of system are:
emollient oils; emulsifiers; humectants; pigment wetting
agents; pigment suspending agents; pigments; pigment
extenders, e.g. talc, kaolin; water; preservatives;
fragrance; additives if required, e.g. vitamins,
sunscreens, etc.

45
TYPES OF FACIAL
MAKE-UP
• II.Face Powders
• These are used to cover minor
imperfections and reduce the shine that
appears on the skin due to sebum or
perspiration.
• They are required to give a matte,
smooth finish to the skin and remain this
way for as long as possible.

• Forms of Face Powders:

• a)Loose Face Powders
• b)Compact Face Powders

46
Whatever the format, the face powder must have the following
characteristics:
1.The powder should have the required covering power to mask minor visible skin
imperfections.
2.It should adhere to the skin and must not be completely dissipated in a short time, so
avoiding frequent re-powdering.
3.The finish given to the skin must complement the skin colour, imparting a velvet or peach-
like character.
4.Shine on or around the nose must be completely eliminated. The powder must be
absorbent without changing its appearance on the skin.
5.There must be sufficient slip to enable the powder to be applied to the skin with a
suitable applicator, such as a puff or brush, without dragging or producing a blotchy effect.
6.The constituents of the powder should be such that a clown-like effect is impossible. The
preference should be towards transparency.

47
TYPES OF FACIAL
MAKE-UP
• III.Two Way Foundation Make-Up
• These are a form of compact powder
foundation that can be applied to the skin
by use of either a wet or dry sponge.
• The overall function is to provide a
natural-looking smooth finish.
• In many ways they combine the properties
of a foundation with that of a face powder,
with extended wear and the potential to
minimize the appearance of wrinkles,
blemishes and skin pores.

48
TYPES OF FACIAL
MAKE-UP
• IV.Blushers
• Blushers, often also called rouges,
are applied to the cheeks, usually
over a foundation make-up, to
emphasize and highlight the cheek
bones. They also give structure to the
face.
• Most are now compressed powders
or emulsions, but previously they
have been available as aqueous gels
that contained water-soluble dyes
which actually stained the skin.

49
 FORMS OF BLUSHERS

a) Pressed Powder Blushers c) Wax-based blushers

b) Liquid blushers d) Bronzing powders

50
 51

TYPES OF DECORATIVE
COSMETIC PRODUCTS

• A. Eye Products
• Eyes are the dominant features of the
face, especially during conversation.
They reflect emotional states as well
as being indicative of our state of
health.
• Modern eye make-up products include
eye liners and pencils for the eyebrows
and to contour the eyes, eyeshadows
of different forms and mascara for the
eyelashes.
TYPES OF EYE
MAKE-UP
• I.Eyeshadow
• Eyeshadow is used to give
colour and gloss to the
eyelids.
• This is the most fashion-
conscious area of decorative
cosmetics, the popular
shades varying with the
season and clothes that are
in fashion at the time.

52
FORMS OF
EYESHADOW
• Pressed powder eyeshadow
• The commonest form of eyeshadows.
• These are sold as single colors in a small
compact with or without an applicator, or as
collections of colors that tone together in larger
compacts or tins with a number of applicators.
• The base ingredients used in pressed powder
eyeshadows are very similar to those used in
face powder. Talc is the main constituent with
zinc stearate to act as a powder binder and also
give skin adhesion.

53
 54

FORMS OF
EYESHADOW
• b)Cream eyeshadow
• This has to be of the correct consistency,
such that it can spread easily on the skin,
but not be greasy or crease during wear,
and the pigments or pearls in the pot or
tube in which they are sold remain
suspended.
FORMS OF
EYESHADOW
• c)Eyeshadow sticks
• These are manufactured using
similar ingredients and methods
of production to lipsticks and
other stick products.

55
TYPES OF EYE
MAKE-UP
• II.Mascara
• The colour, thickness and length of
eyelashes are enhanced by using
suspensions of coloured pigments
in a film-forming medium to which
lengthening ingredients such as
nylon flock can be added.

56
FORMS OF
MASCARA
• Cake mascara
• These were the first type of product
to appear on the market in the 1920s
and are still available today.
• Application is by wetting the brush
and rubbing it onto the cake to pick
up product, and then using the brush
to transfer the product to the lashes.
• Most formulations of this type tend to
have little water resistance and will
smudge if the wearer cries or rubs
her eyes. This is because they are
based on a soap/wax/pigment blend
which is emulsified when the wet
brush is applied to the surface.
FORMS OF
MASCARA
• Cream mascaras
• The most common type of mascara
used today.
• This type is packaged in small thin
plastic bottles with an integral applicator
(or wand) incorporated into the cap.
• The formulations are either oil-in-water
emulsions with a film-former
incorporated, to give water and smudge
resistance, or totally anhydrous, to give
totally waterproof products.

58
FORMS OF
MASCARA

• Waterproof mascaras
• The best way to make something
waterproof is to exclude water
from it totally and use ingredients
that are insoluble in water.
• Waterproof mascaras are
therefore usually solvent-based
systems. The basic solvent has to
be volatile to give a quick-drying
formulation.
59
TYPES OF EYE MAKE-UP

• III. Eyeliners
• These are applied to the rims of the eyelids
following the eyeshadow to accentuate the
shape of the eyes.

• Forms of Eyeliners:
• a)Liquid eyeliners
• b)Pen-Type eyeliners
• c)Eye pencils

60
TYPES OF DECORATIVE
COSMETIC PRODUCTS
• A. Lip Products
• Lip products have been used since ancient
times to enhance the appearance of the lips by
imparting colour and gloss, and by re-defining
the outline of the lips.
• The three most common products used to
achieve this are lipsticks, lipglossesand
lipliners, of which lipsticks are the most
common..

61
RAW MATERIALS USED IN LIP
PRODUCTS

• As we are always licking

our lips, a large proportion
of the product we place on
them we actually eat;
therefore the finished
formulation has to be made
from ingredients that are
edible or suitable for
ingestion and which have
an acceptable taste and
smell.

62
RAW MATERIALS USED IN
LIP PRODUCTS
• i.Oils
• Castor oil is the main oil used in lipsticks. It is
very thick and maintains this viscosity when
hot, making it ideal as a suspending medium
for the colouring agents.
• Oleyl alcohol is a widely used co-solvent in
lipsticks. It aids pigment dispersion and has a
pleasant skin feel and virtually no taste or
odour.

63
RAW MATERIALS USED
IN LIP PRODUCTS

• ii.Waxes
• Waxes are considered as unctuous solids with
different levels of lustre and plasticity.
• In lip products they are used to give structure to
lipsticks and lipliners; they also help them to keep their
form in high temperatures.
• All the waxes used must be flexible but not brittle and
have the ability to retain oils in their crystal structure.
• A combination of hard and soft waxes is used to give
the balance of application and rigidity required by the
consumer.

64
RAW MATERIALS USED
IN LIP PRODUCTS

• iii.Colors
• The colour of the lipstick is the main reason
for its purchase.
• The most popular shades are variations on
types of red, from pinks through to true reds.
• Many lipsticks also contain pearls to give a
high degree of gloss to the lips.
• The lips can either be coloured by covering
them with a suspension of pigment or by
staining them with a dye dissolved in the
lipstick.

65
TYPES OF LIP
PRODUCTS
• I.Lipsticks
• A lipstick, which is by far the commonest
form of lip product, consists of a wedge- or
'bullet'-shaped stick that is moulded hot
and then cooled before being placed into
a small plastic cup or godet, which is held
in a plastic or metal case.
• The godet can be moved up and down
inside the case by a screw or push action.
• When the stick is at the bottom of the case
the whole is sealed by a cap.

66
67

TYPES OF LIP
PRODUCTS
• II.Lip Glosses
• These products are usually far
more liquid than a traditional
lipstick and the use of waxes is
limited.
• They are usually dispensed from
clear tubes to which is fitted either
a rollerball in a housing or a cap
that incorporates a wand with an
applicator attached to the bottom.
TYPES OF LIP PRODUCTS

• III.Lip Liners and Pencils

• These are most often
slim pencils, or fluids
encased in special 'pens'
to which is attached a
fine brush through which
the product is
dispensed, and with
which the outline of the
lips can be drawn.

68
)A+!%Y A,D !'ALUA%&#,: D!"#$A%&'!(
"#)*!%&"(P$#DU"%)

69
 SAFETY AND EVALUATION: DECORATIVE COSMETIC
PRODUCTS

Analysis of cosmetics
includes
1) Physical analysis
2) Microbiological analysis
3) Chemical analysis

70
 EVALUATION: POWDERS

1. FINENESS OF POWDER
◉ Microscopic Method
◉ Air separation technique
◉ Sieving method
- Residue on 75 μ sieve should be NMT 2 %
& 0n 150 μ NMT 0.5 %.

2. APPARENT DENSITY

71
 EVALUATION: POWDERS

3. SHADE AND UNIFORMITY OF SHADE

◉ Comparison with standard shade kept for
this purpose
◉ Commonly std and sample both are placed
between two glassplates and compared
Observed in natural light.

4. ODOR - No physical measure for odor.

72
 EVALUATION: POWDERS

5. PRESSURE APPLIED ON COMPACT POWDER

◉ By Penetrometer

6. BREAKING POINT
◉ Cake is dropped on wooden (8-10 in) or
thick rubber mat (6 feet)

7. MATTER INSOLUBLE IN WATER

◉ Boil 1 gm. with 200ml, filter, dry and check
the residue

73
 EVALUATION: POWDERS

8. MOISTURE AND VOLATILE MATTER

◉ By drying powder at 105 C to constant
weight.

9. pH OF AQUEOUS SOLUTION
◉ By making suspension in water of 10 % or
filtrate may be used.

74
 EVALUATION: POWDERS

10. PAY-OFF
◉ the pay-offcharacter, i.e. adhesionwith the
puff of compact orpressed powder should
betested on the skin

75
 EVALUATION: LIPSTICK

1. MELTING POINT DETERMINATION TEST

• The determination of melting point is done in
order to determine the storage
characteristics of the product. The inciting
point of lipstick base should be between 60
to 65°C in order to avoid the sensati on of
friction or dryness during application. The
method of determination is known as
capillary tube method.

76
Capillary tube method:
(a) In this method, about 50 mg of lipstick is taken and is inserted into a glass
capillary tube open at both ends.
(b) The capillary tube is ice cooled for about hrs and then placed in a beaker
containing hot water and a magnetic stirrer.
(c) The temperature at which material starts moving through the capillary is said
to be the melting point temperature.
(d) Another important parameter is the droop point which determines the
temperature at which the product starts oozing out the oil and becomes
flattened out.
(e) The melting point should be higher than the droop point which determines
the safe handling and storage of finished product.

77
 EVALUATION: LIPSTICK

2. BREAKING LOAD POINT TEST

• This test is done in order to determine the
strength and hardness of the lipstick. In this
method, the lipstick is placed in hori7zontal
position, 1 inch from the base and weights
with increasing loads are attached to it. the
weight at which the lipstick starts breaking,
known as the breaking load point. The test
shall be carried out in specific condition and
at about 25 °C temperatures.

78
 EVALUATION: LIPSTICK

3. DETERMINATION OF THIXOTROPIC
CHARACTER
• This is a test for determining the uniformity
in viscosity of base. The instrument used for
the determination of thixotropic character is
known as the penetrometer.

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 EVALUATION: LIPSTICK

4. TEST FOR APPLICATION FORCE

• This is a test to determine the force to be
applied during application. In this method,
two lipsticks are cut to obtain flat surfaces
which are placed one above other. A smooth
paper is placed between them which is
attached to a dynamometer to determine
force required to pull the paper indicates the
force application.

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 EVALUATION: LIPSTICK

5. DETERMINATION OF SURFACE
CHARACTERISTICS
• The study of surface property of the
product is carried out in order to
check the formation crystal on the
surface or the contamination by
microorganism or formation of
wrinkles and the exudation of liquid.

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 EVALUATION: LIPSTICK

5. DETERMINATION OF COLOR
DISPERSION
• The test is done in order to determine
the uniform dispersion of color particle.
The size of the particle is determined by
the microscopic studies and it should
not be more than 50µ.

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 MICROBIAL ANALYSIS ON COSMETICS

The detection and elimination of microbial Sample preparation for microbiological analysis
contamination of cosmetics is very ◉ For liquid: take 1 ml of liquid and dilute with 9
important to maximize shelf life. It is done to ml of modified letheen broth(MLB) in screw-
ensure product quality, consistency and
cap test tube.
performance and to meet federal
regulations. ◉ Solid and powders: weigh 1 gm of sample in
to screw-cap test tube containing 1 ml sterile
tween 80. Disperse product in tween 80 with
sterile spatula. Add 8 ml sterile MLB and mix
thoroughly.
◉ Wax / fatty products (lipsticks): weigh 10
gm of sample in to sterile tween 20. disperse
with a sterile spatula to form a paste. Add 78
ml sterile MLB and mix thoroughly.
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METHODS FOR MICROBIAL ANALYSIS

A. POUR-PLATE TECHNIQUE
• The sample should be diluted successively
with sterile water. The agar medium is
maintained in molten state at 45˚c. 1 ml of
diluted sample is added to sterile petri dish
to which is then poured 9 ml of sterile, cool
agar medium. The contents are thoroughly
mixed and allowed to solidify. The dish is
incubated at suitable temperature and
conditions. After few days, different kinds of
microbe grow as separate colonies.

84
METHODS FOR MICROBIAL ANALYSIS

B. SPREAD-PLATE TECHNIQUE
• An aliquot of the diluted sample is placed to the agar surface and is
spread uniformly with a sterile bent rod. Incubate it at suitable
temperature and condition. After few days, different kinds of microbes
grow as separate colonies.

85
METHODS FOR MICROBIAL ANALYSIS

B. STREAK-PLATE TECHNIQUE
• In this technique, the sample
is appropriately diluted and a
small aliquot is transferred to
an agar plate. The bacteria
are then distributed evenly
over the surface by a special
streaking technique.

86
METHODS FOR MICROBIAL ANALYSIS

B. MEMBRANE FILTRATION METHOD

• A known amount of pretreated material or
its dilution is passed through membrane
filter assembly. Wash it 3 successive times
each of 100 ml ofbuffered Nacl-peptone
solution. Transfer the membrane on the
surface of solidagar medium in a sterile Petri
dish. The dish is incubated at suitable
temperature and conditions.

87
 CHEMICAL ANALYSIS ON COSMETICS

Chemical analysis of
cosmetics is very important
to ensure that only
permitted ingredient are
added to the product,
information on the label is
correct or not, and to help in
forensic investigation.
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 CHEMICAL ANALYSIS ON COSMETICS

General methods:
i. Determination of methanol in relation to ethanol or 2-propanol by gas
chromatography.
ii. Determination of dichloromethane and 1,1,1 trichloroethane by gas
chromatography.
iii. Determination of chlorobutanol by gas chromatography.
iv. Determination of hexachlorophene by gas chromatography.
v. Determination of water by gas chromatography.
vi. Determination of propylene glycol by gas chromatography.

89
DETERMINATION OF COLORING AGENTS IN
COSMETIC PRODUCTS

• Thin-layer chromatography
• Liquid chromatography
• Spectrophotometry
• Other methods:
- Dyes in lipstick --- Micellar
electrokinetic capillary chromatography
(MEKC) with diode array UV detection

90
ANALYTICAL METHODS USED FOR PRESERVATIVES
IN COSMETICS

1. Ion-pair and reversed-phase LC with UV/Vis detection,

2. Thin layer chromatography (TLC)
3. Capillary electrophoresis (CE)
4. Capillary zone electrophoresis (CZE)
5. Gas chromatography (GC) with flame ionization detector
(FID), electron capture detector (ECD) or mass spectrometry
(MS) detector used for preservative determination

91
 PERFUMERY

• defined by the FDA as a combination of chemicals that gives

a distinct scent
• described in a musical metaphor as having three sets of
notes, making the harmonious scent accord.
The three notes are:
a. Top notes
b. Middle notes
c. Base notes

Top Notes

Middle Notes

Base Notes
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 TOP NOTES MIDDLE NOTES
(Heart NOTES) BASE NOTES
• First notes perceived after applying a
• foundation of a fragrance.
perfume. • Its main body of
• Consist of the most volatile compounds, • long-lasting aromas that
which evaporate very quickly. perfume
usually form accords with
• Short-lived but strong and sharp.
• Act to mask the
• Introduced the wearer to the fragrance and the heart notes.
serve as first impressions. unpleasant initial
• provides a fragrance’s
impression of BASE NOTES longevity and can usually
last for hours.
E.g. sandal wood,
E.g. E.g. vanila,amber
Citrus(lemon,orange),Light Rose,lemon,nutmeg,
fruits(grapes , berries)

94
• Based on Concentration of Fragrance & duration of
lasting.
Class % of Aromatic Duration (hours)
compound
Parfume 20-30 6-8

Eau de Parfume 15-20 4-5

Eau de toilette 5-15 2-3

Eau de cologne 2-4 2

Eau fraiche 1-3 2

96
◉ Men’s fragrances are usually eau de toilette strength.
As alcohol exerts a drying effect upon the skin through its solvent action on
skin’s natural moisturizers and so do toilet waters. There are two ingredients
to counteract this dehydrating effect: emollients, such as light, non-volatile
oils to retard water loss from the skin, and humectants, such as glycerin and
propylene glycol.

◉ Delivery systems for alcoholic fragrances include pump sprays and

pressurized packs, or aerosols. All products in aerosol form must now be
environmentally harmless by containing no cfcs propellant.
• Perfumes can further be classified into following classes:
1 . B r i g h t fl o r a l : Fragrance from one or several flowers.
e.g. Estee lauder’s Beautiful
2. G r e e n : Fragrance from cut grass or leaf.
e.g. Calvin Klein’s Eternity
3 . A q u a t i c : A clean smell reminiscent of ocean.
e.g. Davidoff, Cool Water
4 . C i t r u s : Has freshening effect.
E.g. Faberge Brut
4 . F r u i t y : Aromas of fruits other than citrus.
E.g. Ginestet, Botrytis
6 . G o u r m a n d : Scent with edible or desert like qualities.
E.g. Thierry Mugler’s Angel.
Plant Sources Animal Sources Synthetic
Bark Civet Calone Terpenes
Flowers Honeycomb Argumen Aldehyde
Blossom Deer musk Amber Amyris Calone
Fruits Ambergris
Resins hyraceum
Roots Seed
Wood etc.
Perfumes can be Manufactured by following steps

Collection

Aging Extraction

Blending
10
0
I. Collection:
Before manufacturing process begins the sources of
suitable fragrances are collected in the manufacturing
centre.
II.Extraction:
Oils are extracted from plants and other substances
by several methods like:
a. Steam distillation:
steam is passed through plant materials held in a
still, whereby the essential oil turns to gas. This gas is then
passed through tubes, cooled, liquefied and collected.
b. Solvent extraction:
The flower parts are dissolved in benzene or
petrolatum that retains the fragrance of the flower.
Alcohol is used to dissolve the fragrance and heated to
obtain it after evaporation of alcohol.
c. Enfleurage:
Flowers are kept in glass sheet with grease that
absorb the fragrance of flowers.
d. Expression:
The citrus fruits or plants are manually or
mechanically pressed until all the oil is squeezed out.
III. Blending:
Once the perfume oils are collected, they are ready
to be blended together according to a formula
determined by a master in the field, known as a "nose.”
After the scent has been created, it is mixed with alcohol.
Most full perfumes are made of about 10-20% perfume
oils dissolved in alcohol and a trace of water.
IV. Aging:
Fine perfume is often aged for several months or
even years after blending to ensure that the correct scent
has been achieved.
Perfumes are mainly composed of –
1. Essential oils:
Derived from natural aromatic plant extracts and/or synthetic aromatic chemicals.
E.g. limonene, linalool, geraniol, citral etc.
2. Fixatives:
Natural or synthetic substances used to reduce the evaporation rate. E.g.
benzyl benzoate, benzyl alcohol etc.
3. Solvents:
The liquid in which the perfume oil is dissolved in is usually 98% ethanol
and 2% water.
Alcohol allows fragrance to spread along with it and does not permit microbial
growth in the perfume.
Ingredients Use Side effects

Acetone Solvent Inhalation cause dryness

of mouth & throat

Ethyl Acetate Solvent Defatting effect on skin & may

cause drying & cracking

Benzyl alcohol Fixative Skin irritation ,redness ,pain

Benzyl benzoate Fixative –sweet balsamic odor Skin irritation like-

blisters
Itching,redness.
Sandalwood Fragrance Hypersensitivity

10
5
 QUALITY
ASSURANCE
◉ This requires good instrumentation such as
capillary gas chromatography and possibly with
a coupled mass spectrometer.
◉ Also good manufacturing practice (GMP) in
storage, production and finishing area is
important.
◉ Further, to assure that cross-contamination
does not take place in compounding.
◉ Also stock rotation (to use the old material first).
 QUALITY ASSURANCE
THERMAL STABILITY:
◉ Destruction of perfume molecules is proportionally related to
increase in temperature.
◉ Accelerated storage test, as a measure of the stability of the
product and its fragrance over the much longer period of its
shelf life, in the much cooler environment of its storage and use.
◉ Heat is frequently used during manufacture but the
temperature must be closely controlled to maximize the
efficiency of the process without causing decomposition of the
product.
QUALITY ASSURANCE
PHOTOSENSITIVITY
◉ Sunlight and to a lesser extent the ordinary forms of artificial
light, are in general harmful to aromatic materials, and
perfumed products of all kinds, which must therefore be
protected from light at all times.

◉ Deodorants and Antiperspirants:

Perfumes for these product categories need to be completely
free from any possibility of irritant or sensitizing activity
towards the skin, while imparting fresh and cleanly fragrance
at levels sufficiently modest not to interfere with any personal
perfume being used at the same time
 THE IDEAL SOLVENT
- for use in liquid products should have the following attributes:
- Good solvent for all aromatic materials within a temperature range of –10 to +40.,
- Colorless, preferably mobile, liquid,
- Odorless, Non-flammable, Suitably high volatility,
- In all respects non-toxic and safe to use
- Non-reactive with perfume ingredients Lifting agent for top notes
- Resistant to atmospheric oxidation
- Thermally stable in sunlight, Non-staining
- Miscible with water in all proportions, Non-foaming in water, on shaking
- Readily available at low cost
- Good skin feel (not too oily, not too dry)
- Environmentally acceptable
 COMMON SOLVENTS USED IN PERFUMERY

- Alcohol:
Denatured alcohol of high quality and 96% or 100%
nominal ethanol content is, currently, still the solvent of
choice for most personal fragrances, having the
disadvantages only of flammability, toxicity if abused
and moderate drying effect upon the skin.
- Ethanol is reactive with fragrance materials such as
aldehydes and many esters but since such
interactions are well known and lead to formation of
products of acceptable odor they do not give rise to
problems.
 REferences

◉ ASEAN Cosmetic GMP

◉ Barel A., Paye M. and Maibach H. (2009).
Handbook of Cosmetic Science and Technology,
3rd ed. New York: Informa Healthcare USA, Inc.
◉ Butler, K. (2000). Poucher’s Perfumes, Cosmetics,
and Soaps 10th ed. Great Briatain; Kluwer
Academic Publishers.

111
 REferences

◉ Barel A., Paye M. and Maibach H.

(2009). Handbook of Cosmetic
Science and Technology, 3rd ed. New
York: Informa Healthcare USA, Inc.
◉ Butler, K. (2000). Poucher’s Perfumes,
Cosmetics, and Soaps 10th ed. Great
Briatain; Kluwer Academic Publishers.

112
 REFERENCES

Guidelines for Safety Assessment of Cosmetics

Barel A., Paye M. and Maibach H. (2009). Handbook of Cosmetic Science
and Technology, 3rd ed. New York: Informa Healthcare USA, Inc.
Butler, K. (2000). Poucher’s Perfumes, Cosmetics, and Soaps 10th ed.
Great Briatain; Kluwer Academic Publishers.
Remington’s Pharmaceutical Sciences
Baki, G., & Alexander, K. S. (2015). Introduction to Cosmetic Formulation
and Technology. New Jersey, USA: John Wiley & Sons.
Iwata, H., & Shimada, K. (2013). Formulas, Ingredients and production of
Cosmetics. Tokyo, Japan: Springer Japan.
Tadros, T. F. (2016). Formulations: In Cosmetic and Personal Care. Berlin:
de Gruyter Publisher.
 Thank you!
Any questions?

You can find me at:

username@fatima.edu.ph

#RisetotheTOP

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